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EU MDR Article 61(10) waiver from clinical data

  • 1.  EU MDR Article 61(10) waiver from clinical data

    This message was posted by a user wishing to remain anonymous
    Posted 12-Sep-2023 09:05
    This message was posted by a user wishing to remain anonymous

    EU MDR Article 61(10) provides criteria for waiver from the need for clinical data. Those criteria are based on the results of the manufacturer's risk management and on consideration of the specifics of the interaction between the device and the human body, the intended clinical performance, and manufacturer's claims.

    Yet MDCG 2020-13 Section J instructs notified bodies to call for clinical data as part of the manufacturer's claim that clinical data aren't required.  And I similarly have an Authorized Representative (AR), one rather new to the scene, echoing this as a precondition of representation and registration for a Class I NS/NM/NRSI device. In essence, these interpretations are making a circular argument that clinical data, along with clinical evaluation of those data, are required in order to justify that clinical data aren't required.

    In contrast, I've previously seen a different AR accept an Article 61(10) clinical data waiver without providing clinical data, which is what seems more in line with Article 61(10)'s intent (allowing for the reasonable notion that clinical data aren't always appropriate or needed for demonstration of conformity).  Likewise for example in other jurisdictions like the U.S. and Canada, it is routine to grant marketing authorization for low risk (and oftentimes even moderate risk) devices without clinical data.

    What are your thoughts and experiences about the MDCG's and some ARs assertion that clinical data are required in order to claim that clinical data aren't required?



  • 2.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 13-Sep-2023 03:10

    Hi anon,

    The issue you identified may have to do with the interpretation of MDCG 2020-13. Section J of the CEAR asks for a clinical evaluation, but I do not see where it calls for clinical data as part of the justification to not use clinical data to demonstrate conformity. The CEAR is asking whether the manufacturer has searched for clinical data on their own device and similar devices. I believe it is very reasonable to complete the literature searches for the clinical evaluation as for any other device. Sometimes there are papers mentioning the device under evaluation, there may even be some clinical data. Any clinical data found may be supportive of the device's safety and performance but you would often see that it would be indirect clinical evidence (e.g. success of a procedure in which the device under evaluation was used). I have also seen people use the literature searches to demonstrate that indeed no clinical data are available and it cannot be reasonably expected that trials are done on the type of device (in other words, use searches that return no result as supportive evidence for the 61.10 strategy).

    Regards,

    Wiebe



    ------------------------------
    Wiebe Postma
    Vierpolders
    Netherlands
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  • 3.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 13-Sep-2023 04:07

    Anon,

    This is a widely mis-understood, mis-interpretated, mis-applied, mis-used Article by many individuals, including Notified Bodies.  Whether it is written that way intentionally, written poorly, or just too many variations of interpretations, the concept of when clinical data is needed is not understood.  Indeed as you mention, there are many other regulatory agencies around the world who have the concept of proving the device is safe and performs (effective) using design controls, verification and validation testing (non-clinical), pre-clinical testing, similar devices, literature searches, post market data, etc., then a decision needs to be made whether clinical data is needed.  Unfortunately, the way it is circularly written and mass interpretation of you need clinical data first and then maybe you do not need clinical data if can be justified, not the other way around, leads to much angst currently.  So this is causing many products which have been on the market for a long time and low to moderate risk devices demanding clinical data as part of clinical evaluation.  If more pragmatism was applied, we could probably save having more products on the market in Europe.



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    Richard Vincins ASQ-CQA, MTOPRA, RAC
    Vice President Global Regulatory Affairs
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  • 4.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 13-Sep-2023 11:36

    Thank you, Wiebe for your reply.  Your narrative, "...MDCG 2020-13. Section J of the CEAR asks for a clinical evaluation, but I do not see where it calls for clinical data as part of the justification to not use clinical data to demonstrate conformity..." perfectly demonstrates the dichotomous circularity of the issue:

    "Clinical evaluation" [EU MDR Article 2(44)] fundamentally means a systematic and planned process to continuously generate, collect, analyze and assess the clinical data. Consequently, MDCG 2020-13 Section J's call for clinical evaluation is in effect a call for clinical data.

    Similarly, Section J's questions:

    • "Has any available clinical data for the device or an equivalent device been searched for and/or identified by the manufacturer?", and
    • "...was the identified clinical data integrated in the clinical evaluation", and
    • "Is clinical data available for similar devices, does this provide information with relevant to the safety and performance of the device under evaluation", and
    • "Has the manufacturer conducted an appropriate search of scientific literature?",

    are all calls for clinical data and clinical evaluation.  These clinical data and evaluation requirements placed upon the manufacturer's justification for not needing clinical data again raise the dichotomous nature of the way this is being handled for Europe's Union.  I also note that this dichotomous approach is not new, as it was born out of MEDDEV 2.7/1 revision 4.

    In essence, it seems that clinical data and evaluation are always required for Europe Union's even when they aren't actually necessary for demonstrating conformity with the general safety and performance requirements.  I hope that this paradigm will be reconsidered in realization that burdensome clinical data and evaluation aren't always needed or sensible for the purposes of general safety and performance requirements.



    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    Ridgway, CO
    United States
    © Copyright 2023 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 5.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 15-Sep-2023 03:50

    Hi Kevin,

    Thanks for your insightful comment. I agree with you that there are inconsistencies in the way clinical data and evaluation are required. However, I do think that it makes sense to conduct a clinical evaluation for every medical device, even if the device does not require clinical data. The clinical evaluation is not only used to present and evaluate clinical data, but also to establish the state of the art, demonstrate that various sources were examined for clinical data (a null result is still a result), and to document the strategy for proving clinical safety and performance even if it is decided that clinical data are not deemed appropriate. I believe this is in line with the guidance provided by MDCG 2020-6 and MDCG 2020-5, which explain the purpose and scope of clinical evaluation and how it should be performed and documented. Perhaps the definition of clinical evaluation, which as you rightfully pointed out directly calls for clinical data (i.e. safety/performance data generated from the use of a device) should be broadened to include other data proving the safety and performance of a device.



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    Wiebe Postma
    Vierpolders
    Netherlands
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  • 6.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 15-Sep-2023 12:07
    Edited by Kevin Randall 15-Sep-2023 12:11

    Hello Wiebe,

    Thank you for your narrative, "...it makes sense to conduct a clinical evaluation for every medical device, even if the device does not require clinical data. The clinical evaluation is not only used to present and evaluate clinical data, but also to establish the state of the art, demonstrate that various sources were examined for clinical data (a null result is still a result), and to document the strategy for proving clinical safety and performance even if it is decided that clinical data are not deemed appropriate..."

    Again, statements like, "...it makes sense to conduct a clinical evaluation [i.e., of clinical data] for every medical device, even if the device does not require clinical data..." continue to boggle my mind. Does that not boggle anyone else's mind?

     

    In addition, I question the notion of requiring clinical data / evaluation in order to establish the state-of-the-art.  Indeed, much has been said in this Forum and elsewhere about the meaning of "state-of-the-art"; so, I won't rehash that here.  But in a nutshell, it is current and longstanding precedent (e.g., see MDCG 2021-5, MEDDEV 2.7/1 revision 4, IMDRF, etc.) for Europe's Union that "state-of-the-art" may be demonstrated by means other than clinical data, such as via applicable standards, guidance documents, and experience.  So again, reflexive demands for clinical data to show the state-of-the-art are another overreach in my opinion. It is important to note that MDCG 2020-6 discusses how to establish state-of-the-art for the specific context of devices that require clinical data.  Taking such things out of context can be costly and doesn't undo the other longstanding general precedents for establishing the state-of-the-art via other means, like via applicable standards, guidance documents, and experience, regarding devices for which clinical data are not appropriate.

    Similarly, the notion of demonstrating that various sources were examined for clinical data seems questionable regarding a device for which clinical data are not appropriate.  Maybe there is value in that for business or marketing reasons, but not so much regarding demonstrating conformity with the EU MDR's general safety and performance requirements (GSPR).

    On that note, regarding the demonstration of "clinical safety and performance", I'm unable to locate the notion of "clinical safety and performance" anywhere in the EU MDR. I note that "clinical safety" is mentioned only three times in total, and all in the context of devices that require clinical data.  Accordingly, asserting a need to demonstrate "clinical safety" via clinical evaluation of clinical data regarding devices for which clinical data are not appropriate again raises a circular and overreaching quagmire, at least for regulatory/legislative intents and purposes.  I think we should be careful not to equate demonstration of "clinical safety and performance" with the EU MDR's intent for conformity with "general safety and performance" requirements (GSPR).  While GSPR may sometimes include demonstration of clinical safety via clinical data, it remains that GSPR conformity doesn't always require demonstration of clinical safety [see Article 61(10)].

      

    Thanks also for your given additional examples (e.g., MDCG 2020-6) reiterating Europe's Union practice of demanding clinical data for all devices, even regarding devices for which clinical data are not appropriate. MDCG 2020-6 is indeed another good example of the aforementioned circularity.  Specifically, the ultimate context/purpose/intent of MDCG 2020-6 is to define "sufficient clinical evidence" regarding devices for which clinical data are necessary.  A tease of sensibility is given when, for context, MDCG 2020-6 reminds us that clinical data are not required for all devices and then it recites Article 61(10) accordingly.  But then it goes on to convolute the issue by apparently indicating that clinical data and evaluation are, in some fashion or another, still being demanded regarding devices for which clinical data are not actually appropriate.  It then goes on to exacerbate the issue even further by categorizing three types of non-clinical data (e.g., bench data) as clinical data, consequently making such non-clinical data subject to clinical evaluation.

    I might be able to get accustomed to the awkward semantics of requiring a "clinical evaluation" of non-clinical data as long as the data in that evaluation are just that: non-clinical data.  But what I think pushes over the line into nonsensical regulatory overreach and overburden is requiring clinical data [Article 2(48)] when non-clinical data are sufficient for GSPR.

    MDCG 2020-5 and its attendance to showing clinical "equivalence" between a subject device and a different device are for the context of devices that require clinical data.  Indeed, regarding Article 61(1)'s general requirement for clinical data for all devices, it reminds us of Article 61(10)'s exception to this when MDCG 2020-5 clarifies that, "...It may under certain circumstances be justified to demonstrate conformity without support of clinical data, see MDR, Article 61(10)..."  Therefore, I don't recommend asserting MDCG 2020-5 as a precedent for demanding clinical data regarding devices for which clinical data aren't appropriate.  That would be more overreach in my opinion.

    As a regulatory professional who believes strongly in the principle of a least-burdensome regulatory approach when such an approach is already sufficient for guarding public health, I remain unconvinced about the value and legislative integrity of demanding that every device shall have clinical data and evaluation (i.e., a systematic and planned [and burdensome] process to continuously generate, collect, analyze and assess clinical data).



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    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    Ridgway, CO
    United States
    © Copyright 2023 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 7.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 16-Sep-2023 09:16

    Dear All

    Medical Device Regulation (MDR) is a regulation and not a guidance such as MDCG and MEDDEV. Consequently, the text of the MDR overrules any MDCG or MEDDEV. If the text of the MDCG deviates from the MDR, note this deviation and give the reasoning for the approach taken. Senior individuals at the NBs will/ should accept this approach. 

    The requirement of a clinical evaluation for each medical device are outlined in MDR Article 61 last paragraph: "To that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article and Part A of Annex XIV."

    Clinical data are data which are collected relative to a patient. Consequently, collecting clinical data for medical devices such as medical device steriliser are not possible.

    Addressing Art 61(10) further with respect to "clinical data is not deemed appropriate" would also be associated with situations in which the collection of this data would also put the patient at risk.   

    There are other cases in which non-clinical testing indeed reflects the safety and the effectiveness of the medical device much closer to the reality than the analysed collected clinical data. 

    In the end, we all hope that going forward that the legal requirements will become clearer and the level of understanding at the different junctions will become more aligned. 



    ------------------------------
    Stephanie Grassmann
    Founder & Managing Director of MedTechXperts Ltd
    Biberstein
    Switzerland
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  • 8.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 17-Sep-2023 04:57
    Edited by Ronald Boumans 17-Sep-2023 04:57

    In my view this is a rather simple issue: there is a difference in the meaning of clinical data and the clinical evaluation. Clinical data, see definition 48 of the MDR, is about data coming from the use of the device. The clinical evaluation is about the acceptability of risks when weighed against the clinical benefits. This does not necessarily have to depend on clinical data. For example, an accessory may use validation testing to demonstrate that the claimed performance is delivered. That test result can be used in the clinical evaluation of this accessory. 

    This is something I would typically expect to see in the regulatory strategy report. By providing such information to any reviewer, they either have the discussion then, or you manage their expectations in such a way that they accept this principle. Regulatory strategy: make sure the problems are addressed right at the start.



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    Ronald Boumans
    MDR Expert
    Super PRRC
    Netherlands
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  • 9.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 18-Sep-2023 12:06

    Pursuant to the aforesaid definition of "clinical evaluation" in Article 2(44), the legislative intent is that clinical evaluation fundamentally and necessarily involves evaluation of "clinical data".  And "clinical data" is not a term that is eligible for our subjective interpretations; instead, it has a longstanding, standardized, and now legislative, meaning [definition in Article 2(48)].  Legislatively speaking, "clinical data" does not include non-clinical data.  An evaluation of non-clinical data is not clinical evaluation, but rather is non-clinical evaluation that may consist of a variety of non-clinical methods pursuant to Annex II.4(b) and Annex II.6.  Accordingly, if we include an evaluation of non-clinical validation data (or other non-clinical data) under the guise of clinical evaluation, then we would be out of step with the legislative intent of Europe's MDR for clinical evaluation.  Moreover, Europe's MDR has been a burdensome leap for the device industry and regulators alike. Magnifying that burden by deploying clinical evaluation (itself a considerable burden all its own) for the assessment of non-clinical data is not only incongruous with legislation, but also drives up regulatory costs considerably.



    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    Ridgway, CO
    United States
    © Copyright 2023 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 10.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 19-Sep-2023 03:37

    Dear Everyone,

    I hope this message finds you well. I wanted to share some thoughts on our ongoing discussion, particularly regarding the interpretation of MDCG guidelines.

    First and foremost, I'd like to express my enthusiasm for MDCG 2020-13 J, as it provides the necessary guidance we need. Without this reference, we might encounter situations where notified bodies could question the applicability of Article 61.10 for medical devices. This is a pivotal concern because, in general, medical devices with potential risks and hopefully clinical benefits require a robust clinical evaluation. However, under the guidance, we have the means to justify that further "clinical data is not deemed appropriate."

    The MDR explicitly mentions when "clinical data is not deemed appropriate." Two scenarios come to mind:

    1.     The device is not a medical device, which implies that obtaining clinical data is simply impossible due to the absence of clinical benefits. This category typically includes accessories, especially those that do not interact with the patient. Accessories that do interact with the patient may need to follow the suggestions outlined in Article 61.9 regarding required data.

    2.     In cases where the device is indeed a medical device, there may be situations where it's not deemed appropriate to obtain additional clinical data. Here, Article 61.6(b) can be a valuable resource, particularly when dealing with well-established technologies.

    It seems that MDCG 2020-13 predominantly refers to the second scenario, strongly suggesting that it's appropriate for medical devices to apply Article 61.10. This is indeed a valuable reference, and I believe we should celebrate its existence.

    For scenario one, conducting a clinical investigation is not even be ethically justifiable, and a clinical evaluation and Post-Market Clinical Follow-up (PMCF) should not be necessary. In contrast, for scenario two, while a clinical investigation might not be mandatory, it might still be essential to continue the clinical evaluation process. And certainly Post-Market Surveillance (PMS) is sufficient instead of a PMCF. However, these decisions should be made within the context of a thorough evaluation that indeed the conformity with the general safety and performance requirements is given.

    In conclusion, it's worth considering that the Commission could significantly assist in this matter by implementing Common Specifications (CS) to establish standardized clinical data requirements for all devices, particularly those involving well-established products. This would eliminate the need for manufacturers to speculate about what constitutes sufficient clinical data, as everyone would adhere to the same principles. I hope that the MDCG will prioritize this direction, and manufacturers could potentially influence this positive shift, ultimately resolving a substantial issue in our industry.

    Warm regards,



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    Ludger Moeller
    President, MDSS GmbH
    l.moeller@mdssar.com
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  • 11.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 19-Sep-2023 09:37
    Edited by Kevin Randall 19-Sep-2023 09:49

    Thank you Ludger for your insights and narrative stating that MDCG 2020-13 J, "provides the necessary guidance we need".  MDCG 2020-13 J was discussed earlier in this thread and it calls for clinical data for all devices, even those for which clinical data aren't appropriate.  Could you elaborate further on which aspects of MDCG 2020-13 J you feel provide the necessary guidance we need?

    Article 61(6)(b) provides an exemption from "clinical investigation" [Article 2(45)].  It does not provide an exemption from "clinical data" [Article 2(48)].  Indeed, Article 61(6)(b) specifically demands sufficient clinical data for the Article 61(6)(b) devices. Could you elaborate further on how Article 61(6)(b) which requires sufficient clinical data applies to Article 61(10) devices which instead may be shown to conform with GSPR based on non-clinical data alone?


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    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    Ridgway, CO
    United States
    © Copyright 2023 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 12.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 19-Sep-2023 10:52

    Hi Anon,

    a little late, but to come back to your original question:

    What was the justification of the AR with respect to MDCG 2020-13 section J to call for clinical data? Section J seems to refer to Article 61(10) and then ask the notified body (as this is a template for the NBs clinical evaluation assessment report) to consider if clinical data (for the device, an equivalent device or similar devices) has been searched for (and if yes, if the data was evaluated). As far as I can see you could answer both questions with "no" and still have a rationale why this was the case. Or you might have searched for clinical data but not have found any - again I do not see anything in the guidance prohibiting that.

    There is a lot of valid concerns within this thread and a many things can be said about the wording and consistency of the MDR and the accompanying interpretations by the different actors including the MDCG. However, for a concrete case it might be more helpful to analyse the exact argument and ensure that there is no misunderstanding before going into a more general discussion (that is nevertheless required and makes sense in the overall context to avoid having these detailed discussions in the long run).

    So if you think it might help you argue for your specific case with this AR: Maybe share their more detailed argument and we can see if there is a way to resolve that on a more individual level.

    Best regards

    Christoph



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    Christoph Kiesselbach
    Reutlingen
    Germany
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  • 13.  RE: EU MDR Article 61(10) waiver from clinical data

    Posted 19-Sep-2023 11:09

    Hi all,

    on a more general note: One resource for a discussion of this topic is a BSI on demand webinar specifically discussing Article 61(10) from their point of view that was part of their clinical masterclass series. It should be available under https://www.bsigroup.com/en-GB/medical-devices/resources/webinars/ (there is some sort of registration required). 

    Best regards

    Christoph



    ------------------------------
    Christoph Kiesselbach
    Reutlingen
    Germany
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