Name: Clinical Evaluation for Medical Devices
Uploaded: 2026-11-03T16:08:05.741Z
Duration: 49 min
Description: Clinical Evaluation for Medical Devices

Transcript for "Clinical Evaluation for Medical Devices": So hello, and welcome to today's webinar on clinic evaluation for medical devices. My name is Claudia Bang, and I'm a senior consultant in medical devices, with a focus on clinical affairs and, yeah, biological safety. So before we begin, let me briefly introduce, myself. So, I've been working at NSF since 2017, and I'm part of the clinical affairs team. So my main area, of areas of ex... Peer expertise include clinic evaluation, clinic investigations, PMCF, and also biological safety. I support manufacturers throughout the device life cycle, and also provide training on clinical and regulatory topics. And today, I would like to share both the regulatory perspective and and some practical observations from clinical evaluation projects. So, let me let me also briefly introduce NSF, my company. So NSF was founded in 1944 with the mission of, improving human and, planet health. And today, we're expert support support organizations, around the world and, with with science based services and practical industry knowledge. NSF focus on three core industries, so food and nutrition, water and life sciences supported by additional enterprise solutions. And today, we will focus on our life sciences activity and in particular, our support for medical device manufacturers. So within, life sciences, NSF provides, yeah, services for audits, consulting, documentation support, and, training across pharmaceuticals, combination products, medical devices, and also IVDs. We support medical device manufacturers throughout the, whole product life cycle, so from regulatory strategy, product development, to clinical affairs, technical documentation, manufacturing, and post market surveillance. And our service portfolio is certified according to ISO, 14, four eight, five. And please note that this presentation reflects information available at the time at, the presentation. And, so, this is to today's agenda. So we will begin with the purpose of clinic evaluation and the main areas of, focus and notified bodies, reviews. We would then look in at the, MDR 2.0 proposal. So I included this topic because manufacturers need to comply with today's requirements, while also preparing for possible future changes. And, the proposal could affect important clinical evidence pathways, so we will consider what may change, what would remain, and what manufacturers, can already do without implementing the proposal prematurely. And we will conclude with the main takeaways and practical actions manufacturers can consider today. Practical actions manufacturers can consider today. So let us start with the fundamental question, why do we perform clinical evaluations in, the first place? At its core, clinic evaluation demonstrate that a device is safe, performs as intended, and provides meaningful, clinical benefit. It is not simply, about preparing a clinical relation report or CUR for regulatory submission, but about continuously confirming conformity throughout the device life cycle. This requires evidence from different different sources, including clinic investigations, scientific literature, PMS, so post market surveillance, PMCF, post market clinical follow-up, and with justified, equivalent devices. So the clinical relation brings these sources together into one cons... Consistent benefit risk assessment. Yeah. Let us now look at how these activities, yeah, connect to the device life cycle. So this slide shows, clinical evaluation as a continuous process with five connected steps. So we begin by defining the scope, claims, and evidence requirements in a clinical evaluation plan, the CEP. We then identify the available clinical data, appraise, their relevance and quality, and analyze, the overall evidence to reach conclusions on safety, performance, clinical benefits, and benefit risk. The process does not end when the clinical evaluation reports or the CER is completed. So PMS and PMC, have findings continue... Continuously feedback into the clinical evaluation and may and may lead to updated conclusions, new evidence, needs, or changes to the plan. The regulatory references, shown, here below provide a framework for this life cycle process. And important point is that, clinical relation connects clinical evidence, risk management, PMS, and PMCF. Let us now look at what a notified bodies, typically focus on when accessing whether this process is sufficiently, robust. So based on our practical observations, four topics frequently arise during notified bodies, reviews. This is a meaningful clinical outcomes or... And sufficient evidence, reproducible literature search and Cune state of the art, consistent claims and documentation, and an appropriate, PMCF, so post market clinical follow-up strategy. The specific findings may vary depending on the device and, of course, available evidence, but these four areas recure regulatory... Regularly in our work. The common topic is traceability. So the intended purpose and claims, should be clearly linked to the outcomes, supporting evidence, benefit risk, conclusion, and post market activities. Let us, look at these areas in more detail, starting with outcomes and clinical evidence. Yeah. The central question is whether the clinical, success criteria are clearly defined, measurable, and appropriately, supported by the available evidence. This process, begins in a clinical relation plan. So the key requirements, as you probably all know or heard about, is that the CEP should specify specify the relevant outcomes for safety, performance, and clinical benefit. So these outcomes should be linked to the intended purpose and the claims, made for the device. The related acceptance criteria, need need to be quantitative, clinically meaningful, and justified in relation to the state of the art. So in other words, manufacturers should not only define what will be assessed, but also, explain what level of performance, or clinical benefit would be considered acceptable and why. Common findings, we we observed in our daily work, include missing or unclear acceptance criteria, outcome parameters that were not defined in, the CEP, or criteria that cannot be linked to appropriate benchmark or similar or state of the art. In such cases, it becomes becomes difficult difficult to determine objectively whether the clinical evidence is sufficient. So a practical approach, is there of to define relevant outcomes and measurable acceptance criteria before evaluating the evidence. The clinical evaluation report should then clearly demonstrate whether each criterion has been met and whether the, evidence supports the related device claims. And finally, the conclusion should be traceable from the device claims, through the predefined outcomes and acceptance criteria to the actual clinical evidence. Yeah. This slide shows, the pathway from clinical evaluation planning to the finance, CER conclusion. So this is a kind of a strategy how you can defined, define your outcome parameter and acceptance criteria. So, clinically relevant outcome parameters are defined in the CEP based on the device claims and the state of the art, and each outcome is linked to a quantitative and measurable acceptance criteria. And this may be, a range, a minimum, a minimum or maximum value, a mean, or a weighted mean. The available clinical evidence for the device and were justified, an equivalent device is then assessed against, these predefined criteria. The CER should clearly show with evidence, supports each outcome whether the criterion is met and whether the, corresponding safety performance or clinical benefit claim is supported. So let us look at a simplified example to illustrate how an outcome parameter acceptance criteria... Criterion and a device specific evidence, can be linked. So the selected outcome in the slide is, the revision rate following total hip atroplasty and based on the state of the art, a maximum revision rate of 50 has been defined, while the device specific evidence shows rate of ten percent. So this means the acceptance criterion is thereof met. However, comparing, the percentages alone is not sufficient. The patient, populations, indications, follow-up periods, definitions, statistical methods must also be sufficiently comparable. The key point is that acceptance criterion should be justify... Justified based on the state of the art and defined before the device specific evidence is assessed. And this highlights also the importance of a good literature search, which will be the next, yeah, topic. The central questions are whether the literature search can be reproduced and whether the clinical acceptance criteria are supported by a current and relevant state of the art. The literature search, yeah, the requirements are that the literature search should be systematic and objective and should identify both favorable and unfavorable data. The search protocol should clearly... Should also clearly, define research questions, question databases, the search terms, the search dates, selection criterion... Criteria, and also the appraisal methods. So a reviewer should be able to understand how the results were obtained and, in principle, repeat to to search. It is also important to distinguish between different purposes of the literature. So literature relating directly to the device and evaluation has a different role from literature used to establish the state of the art. The state of the art search should also consider alternatives, similar benchmark devices, accept an... Accepted clinical practices, and cure and safety and performance level. Common findings, we observed are, for example, incomplete search documentation, missing elements of the PICO framework, unclear screening methods, or lack of predefined relevance criteria. Another issue is that, device specific literature and state of the art literature are not clearly separated, and searches may also be outdated or may not, may omit relevant alternatives and similar benchmark devices. Manufacturers can address this issue by using a clearly documented and reproducible search protocol. It can also be helpful to map each literature, source to its intended, to its intended purpose, such as evidence for the device, an equivalent or similar device to state of the art or an alternative treatment. And finally, the literature search should not remain static, so manufacturers should, define when it's need... When it needs to be updated. For example, because of new clinical, knowledge and newest, relevant product changes or the passage of time. So once the relevant evidence and, yeah, benchmark have been identified, The next challenge is to ensure that the residing claims are supported and presented consistently across all or all relevant documents. The third, topic or area is the management of claims and their consistency across, just the technical documentation. And the central question is you whether every clinical statement can be traced back to supporting evidence and whether the statement appears consistently across, the relevant documents. So create claims relating to the intended to the intended purpose, safety, performance, or clinical benefit must not be misleading as you, all know. So in particular, clinical claims and the benefit risk conclusions need to be supported, by sufficient clinical data. This consistency needs, needs to extend beyond the clinical evaluation report, So the intended population indications, contraindication warnings, device versions, should be aligned across the CER, the risk management documentation, the instruction for use as a CP, PMS, PMCF document... Mention... Documentation and relevant marketing materials. Common findings regarding claims and consistency across documents, include that, claims, are not clearly listed, classified, or evaluated in a CER. In other cases, the marked, the market clinical benefit is brought out and a benefit actually supported by the evidence, and, inconsistencies may also arise when different documents refer to different patient population, indications, warnings, or device versions. A practical manufacturer strategy is, or could be to establish a controlled claim, inventory. Each claim, could be linked to, an owner, the required evidence type, the supporting source, and trigger for review during the product life cycle. A document consistency matrix can then be used to verify that each claim is presented consistently across the specific... Across the relevant documentations. And this becomes, important when clinical evidence, risk information, product specification, or the intended purpose change. So the key message is that technical documentation should tell one consistent and evidence based story. So a claim should not appear in marketing materials, for example, if it cannot be tracked back to the clinical evidence and the conclusion of the CER. The fourth area is the post market clinical follow-up, so the PMCF. The central question is whether the post market evidence closes the loop and continuously feeds back into the clinic evaluation. PMCF should not be viewed as a separate or or onetime activity. It is it is a continuous process used to confirm safety performance, and, of course, clinical benefit throughout the expected lifetime of the device. And it should, also help identify previously unknown risk, monitor unknown risk, and address any remaining gaps or uncertainties in the clinical evidence. So, the PMCF plan should, therefore define proactive and device specific methods, key objectives, appropriate timelines, and a suitable approach for analyzing the results. The selected activities should be proportionate to the device, its risk profile, the available clinical evidence, and, the reigning... And the remaining clinical questions. Other common findings, we observed regarding PMCF include that PMCF activities are too general, so passive or insufficient for the device and its expected lifetime. In other cases, PMCF is missing from the overall clinical developmental strategy or the justification for the selected approach is not convincing. And plans may also be outdated or the methods and timelines may not be clearly justified. So manufacturers should, select, methods that directly address to identify evidence needs depending on the device and the open questions. This could induce, include, yeah, registry data, a targeted user or patient survey, or PMCF investigation. And finally, the results should not remain isolated in a PMCF report. They should report. They should feedback into the CUR, also... But also risk management documentation and PMS, SSCP, and our relevant outputs. And this feedback is what closes the clinic evaluation loop. Bringing these four focus areas together, there are five practical, steps, manufacturers can do to prepare a more, consistent and trace... Traceable, clinical evidence package. So, yeah, manufacturers should prepare the clinical evidence package as one controlled and connected clinical story. The practical takeaway, can be summarized in five actions. So define, trace, align, challenge, and update. So define the clinical framework, link every claim and risk to supporting evidence, keep all documents aligned, critically review, the package before submission, and continuously update the clinical relation using literature, PMS, and PMCF. So the key message is that completeness completeness alone is not enough. So the entire evidence package must be consistent and traceable. So let us now turn to, sorry, the MDR 2.0 proposal. Yeah. For the targeted version of the MDR and IVD framework. So this is the correct site. So sorry. I have to again. Okay. So the proposal was presented in December 2025 and is being considered under the legislative procedure, and it aims to simplify the existing framework and reduce unnecessary regulatory and administrative burden by maintaining a high level of patient and public health protection. And the main policy objectives include greater greater proportionality, lower administrative cost, faster access to safe and innovative medical devices, and the proposal also seeks to improve the predictability and efficiency of certification processes, provide better support for innovation and special patient needs, and stronger coordination and digitalization. Another objective is to improve alignment with the related European legislation and support international cooperation. And the core idea is thereof not to, reduce the required level of safety. It is, to make the regulatory framework more proportionate, predictable, and efficient while preserving a high level of health protection. However, one point is essential. This is a legislative proposal and not yet applicable law. So its provision may still change as the proposal moves through the legislative process. So, therefore, manufacturers should monitor its development, but should not yet treat the proposed provisions as binding requirements. So this leads to the next question. When, could, the proposed changes actually become applicable? And there's currently new... No confirmed application date. So the u... European Parliament and the council first need to review, negotiate, and agree on the final text. And after formal adoption, the regulation must be published in the official, journal and enter into force. So specific provisions may then apply immediately or after transitional periods. Yeah. And as the legislative timeline is not yet confirmed, the slide presents three illustrative planning planning scenarios, and publication could occur in late twenty twenty six. So... Or early twenty seven under an optimistic scenario during 2027 under the base case or during, during 2028 if negotiation take longer. So so you or manufacturers could use this scenario only for preliminary data, planning and update their timelines once the final tax, the application date, and transitional provisions are known. Sorry. Yep. So let us now look at the key proposed changes. One of the proposed changes that are, that are relevant or is relevant to the clinical to clinical evidence requirements is the scope of article 61 paragraph four. So under the current, MDR wording, clinical investigations are required for implantable devices and class, free devices unless one of the specified exceptions applies. So because wording refers body to implantable devices, it, can be read as, covering implantable devices regardless of, whether they are classified as class two a, class two b, or class three. And the proposed wording is more specific, so it prefers to implantable class two devices and class, three devices while expressly, while, excluding custom made devices. So the practical effect would be a narrower and more clearly defined scope. So implant wheel class two a devices would no longer fall within the automatic clinical investigation expectation established by paragraph four. So the specific requirement, would, instead focus on implantable class two a devices, implantable class two b devices, and class three devices. However, does the... That... However, this does not mean that implantable class two devices would no longer require, sufficient clinical evidence. This would mean a subject. This would remain subject to the general, clinical evaluation requirements of article 61. So, the key distinction is thereof between an automatic exception on article 61 paragraph four and the broader application to generate sufficient clinical evidence to demonstrate conformity. So the main exceptions under article 61 paragraph four, that allowed manufacturers not to conduct a clinical investigation remain unchanged. So for the same manufacturer modification route, the manufacturer must demonstrate appropriate equivalence, provide sufficient clinical evidence evidence, and establish a suitable PMCF plan that includes appropriate post market, studies. And, yeah, these, conditions work together. So these are not three separate exempt... Three separate exemptions. They are connected, conditions that need to be considered together when relying on the same manufacturer's modification board. So in principle, the additional exemptions under article sixty one six would remain, but the proposed wording provides further clarification on their scope and application, but we will come to it later. So the practical message, is that relying on an exception does not remove the need for a clinical relation strategy. So the manufacturer still needs to demonstrate equal... Equivalence, equivalence, provide sufficient clinical evidence and establish an appropriate PMCF approach. So what, would this proposed, what was... Would, this proposed change, mean in practice? So clinical investigation would remain in the default, for implantable class two b and class, three devices unless an an applicable, exception can be demonstrated. The existing modification and equivalence route would remain available, provided that sufficient clinical evidence and appropriate PMCF activities are in place. And at the same time, yes, several several uncertainties or questions, remain open from this, proposal. So, however, no automatic requirement does not mean no clinical investigation. And if relevant evident... Evidence gaps remain, new clinic data may still be needed. The appropriate strategy will depend on a specific device, its technology status, and applicable regulatory, requirement. So let us now look at the proposed change to articles 61, paragraph five, concerning equivalence to a device from another manufacturer. Under the cure in MDR, the manufacturer must demonstrate, equivalence, and have a contract that provides ongoing access to the equivalent device, technical documentation, and the original clinic evaluation must also comply with the MDR. The proposal would remove the requirement for contract, as you can see here on the right side, and ongoing full access to the technical documentation. However, the manufacturers would still need to demonstrate equivalence to the marked, device in accordance with annex 14. And in addition, the manufacturers would need to provide clear evidence to the notified body that original clinic evaluation was performed in compliance with the MDR. So the key change is there of the removal of the, contractual access requirements. The underlying clinical evidence requirements do not appear. So the manufacturers would still need to... Would still need enough reliable inform... Information, to demonstrate equivalence equivalence and, support the clinical relation. This could make it easier to use a device from another manufacturer manufacturer as an equivalent device, but the practical evidence threshold remains an important, yeah, open question. So what could this proposed change mean in practice? So equivalence to a competitor device could become more feasibility because, this formal agreement with the other manufacturer would no longer be required. Where sufficient evidence is available, this could reduce the need for a new clinic investigation. However, manufacturers must still demonstrate technical, biological, and clinical equivalence, and provide clear evidence that original clinical relation, complied... Is, complied with the MDR. A notified body discussion may therefore, focus more on the completeness, reliability, and quality of the available evidence. Open questions, remain, regarding the information needed to verify the original clinical evaluation, the level of evidence, that notified bodies will accept. Manufacturers should, thereof, assess this pathway carefully and not assume that, available information alone will be sufficient. In addition to the proposed change to article 61 paragraph five, the proposal would also modify the equivalence criteria, and annex... In annex, 14. So under the CU and m d... CU and MDR equivalence must be demonstrated on the basis of technical, biological, and clinical characteristic, and these three dimensions would continue to apply. So the technical criteria would remain largely unchanged, so devices would still need to have comparable design characteristics, condition of use, specification, properties, and principle of of operations. The main changes concern the biological and clinical criteria. For biological equivalence, the queue and reference to the same material or substances, would be broadened to the same or similar materials or substances. However, the tissue or body fluid contact, duration of contact, and release characteristic would still need to be comparable. For clinical equivalence, equivalence, the device could be used for the same or a similar clinical condition or purpose. So the remaining clinical comparison criteria would continue to apply. Importantly, this flexibility, would not would not remove the need for, scientific assessment. Any identified differences would need, to be evaluated and shown not to result in clinically significant differences in safety and clinical performance. So the proposal would, they have broadened the comparison criteria, but not lower the required quality of, equivalence, equivalence demonstration. What could these changes mean in practice? So in practice, the broader wording may expand, the range of potential equivalent devices and provide access to additional clinical evidence. However, manufacturers must still assess all technical, biological, and clinical differences and demonstrate that they are not clinically, significant. Sufficiently detailed and reliable data remain essential as, available information may not support, equivalence claim equivalence claim. And, yeah, also some open questions remain, regarding the interpretation of same or similar to required evidence and sufficient data access. And, yeah, further guidance may be needed to... And equivalence should continue to be assessed, case by case. Let us now look at the ex... Exemptions under article 61 paragraph six. As discussed earlier, the proposal would clarify that this paragraph applies to, yeah, implantable class two b devices and class three devices. The first exemption under point a would remain largely unchanged. It connects, con... It concerns, the legacy devices that were, yeah, placed on the market under the previous directives and meet the applicable conditions. The main change concerns point b. Under the current MDR, this exemption refers to fixed list of device types, including including, for example, dental fillings, plates, clips, and connectors. And the proposal would replace this fixed list with the broad... Broader category of, well established, technology devices or or red devices. And to use these exemptions, the clinical relation would need to be based on sufficient clinical evidence and comply with any relevant product specific COM specification where available. The term would also change from sufficient clinical data to sufficient, clinical evidence, and this reflects a broader assessment of the complete evidence based rather than individual clinical data sources alone. So the main changes thereof move from a fixed product, list to a criteria based category. And, yeah, whether a device qualifies would depend on, whether it meets, the proposed definition of a well established technology device. So the proposal would also introduce this, definition of a established technology device in article, two, paragraph, points 72. Importantly, the assessment would be made at the level of the relevant generic device group. So a device could qualify only if it belongs to a generic device group that meets all four proposed criteria. So first, the device group must have a simple, calm, and stable design. And second, the device group must not have been associated with safety issues in the past. Third, the clinical performance must be well known. And finally, the device group must not have a long history on... Must have a long history on a European market. So all four criteria must, is... Would need to be met, and a long market history alone, for example, would not be sufficient if the design has changed changed, or relevant safety concerns have been identified. Because this assessment takes place at the level of the generic device group, the definition of that group becomes, also very important, and the proposal would replace or with end the definition of a generic device group. So devices would thereof need both the same or similar intended purpose and a common technology. So this is important because that wet status, would be assessed at the group level, meaning that the definition and justification of the group could directly affect, whether a device qualifies. So what could this, could these proposed changes mean in in practice? So replacing the fixed product list with wet criteria could load more major device groups to qualify for the clinical investigation exemptions. However, generic device groups may need to be defined more narrowly and consistently based on intended purpose purpose and common technology, and wet status may support a more, pro... Proportionate evidence strategy, but clinical relation and sufficient clinical evidence remain, required. How manufacturers would need a documented justification covering design, stability, market and safety history, clinical performance, and state of the art? Open questions, remain regarding the device grouping, evidence, thresholds, and assessment of sufficient clinical evidence. And further guidance may therefore be needed, and manufacturers should not assume that a major or long established device automatically qualifies. I would also briefly highlight a few additional, proposed changes, of this MDR 2.0. So the proposal would provide greater flexibility in a clinical evidence pathway, including more recognition of nonclinical methods such as in vitro, Insilico, and assimilation based approaches. It would also introduce a concept of a clinical developmental strategy. However, these alternative approaches would still require a scientific justification, and a clinic aiolation would remain mandatory. Furthermore, expert panel advice, would remain nonbinding, but any deviation would need to be justified. In addition, PMCF results, would be incorporated directly into the CER and technical document... Documentation instead of being documented in a separate PMCF evaluation reports, and updates would also become, yeah, relevance based rather than following a fixed annual sketching... Schedule regarding PMCF data. So, overall, these changes could reduce duplication while clear documentation and traceability would remain essential. So having reviewed the main proposed, yeah, changes, let us now move to the key takeaways and practical consideration for, for the manufacturers. So to summarize, the proposal could introduce more targeted and proportionate clinical evidence requirements. Clinic investigation requirements could become more focused, while equivalence could become more flexible through broader biological and clinical comparison criteria. And a proposal could also support, greater greater use of justified nonclinical evidence and more integrated clinical documentation. However, as I said, these are proposed, changes only. And, yeah, the MDR proposes not yet applicable law, so... And manufacturers must continue to comply fully with the Q and MDR. So despite the proposed changes, the core requirements, would would remain. So clinical evaluation would continue to to be mandatory throughout the device life cycle supported by clinical meaningful outcomes, measurable acceptance criteria, and sufficient evidence. Equivalence would still require, such scientific justification, and literature surveillance, PMS, PMCF, would remain important for maintaining the clinic evaluation. Consistency and traceability across the techno... Technical documentation would also remain essential. The device pathway may thereof become more proportionate, but need for, a good clinic evaluation would not change. So what should manufacturers do while, the legislative process is still ongoing? So manufacturers should prepare for possible changes without applying the proposed provisions too early. So first, continue to comply fully with the queue and MDR and monitor the legislative process, including the final wording and any transitional provisions. At the same time, manufacturers can assess which devices, evidence, pathways, and documents could be affected. They can also begin reviewing potential wet status, equivalent strategies, possible application of article 61 paragraph 10. However, procedures should only be changed once the final legal requirements and application dates are confirmed. So the practice message is comply now, assess the potential impact, prepare the evidence, and implement, yeah, later. Yeah. Before we, close, I would like to share some additional resources for medical device... For you, for the medical device manufacturers. So these, materials provide further information on regulatory compliance, technical documentation, and also clinical affairs services. And I would also like to briefly highlight an upcoming opportunity to meet, and exchange ideas in person. So on November 12, we will be hosting the NSF medical, device summit in Hamburg Hamburg. Oh, Hamburg. If you're interested, you can scan... You can use the QR code to view the full agenda and register for free, for the event. Yeah. So... And, as you probably know, NSF also offers further webinars on different topics. So you can also check the link or scan a QR code, if you like. And, this brings me to to the end of today's presentation. Thank you very much for your time and attention. And you can find further information or general... And our general contact details here, and my personal contact information is shown below, is shown on the next slide. So please feel free to contact me if you would like to discuss any of today's topics in more detail. And if you have any questions, please post them in the chat. I would like to, yeah, be happy or I'm happy to, yeah, follow-up with, the... With an email. So thank you very much.