Regulatory Open Forum

Dear all,

Probably I'm wrong, but I'm not so sure that this MDCG guidelines are "only guidelines". 

For my understanding the Auditor asked for what is stated in MDR. I don't consider this request "poor" but  absolutely appropriate  "clarify where the evidence for using and considering MDCG guidelines can be found "

ANNEX VII REQUIREMENTS TO BE MET BY NOTIFIED BODIES, in article related to "Conformity assessment activities" it is clearly stated: the notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.

The notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.

For Clinical evaluation assessment in particular, it is stated that: These procedures referred to in the first paragraph shall take into consideration available CS, guidance and best practice documents.

Also the Article 105 of MDR list of all task of the MDCG.

In particular (c), (d) and (e) are interesting in device development. I list them below.

(c)        to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;

(d)        to contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation (EU) 2017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex I to this Regulation;

(e)        to contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;

In article 106 it is also stated: The clinical evaluation guidance referred to in point (c) of paragraph 10 shall be published following consultation with the MDCG.

paragraph 10 (c) : (c) to develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;

It would probably be advisable to seek the advice of some lawyer.

Best regards,

K

Indeed Katarzyna, it is not uncommon for NBs and other parties to assert more weight to guidance documents than what is fundamentally intended for guidance documents. This is no surprise in light of narratives like those in MDCG 2019-6 which can seem conflicting.  For example, all in one paragraph, MDCG 2019-6 states, "…guidance documents are by definition not compulsory…", yet then goes on to say, "…However, all guidance documents endorsed by the MDCG reflect the interpretation of the EU law jointly agreed by the authorities which are in charge of interpreting and applying the EU law.  Hence notified bodies should be encouraged to apply these guidance documents (also taking into consideration Section 1.6.2 of Annex VII to the MDR/IVDR1).  Furthermore, it is to be noticed that the European Court of Justice often refers to guidance documents when developing its rulings. Hence Notified Bodies have an interest, also in terms of liability risk, to follow that guidance…".

I contend that the forgoing MDCG 2019-6 narrative and similar ones from EU MDR Annex VII are recommendations for NBs in the context of their unique role as conformity assessment bodies, and thus tangential to NB liability as unique and distinguished from the manufacturer's liability.  Accordingly, it is not surprising, and is probably for good measure, that conformity assessment bodies assert accepted guidelines as a baseline during conformity assessments.  But regardless of such baseline practices by NBs, MDCG 2019-6 nevertheless ultimately reminds us of an important boundary:  Non-conformities will not be raised against standards or guidance but need to be phrased against legal requirements.

Accordingly, the fundamental purpose of guidelines remains intact, as do the basic intentions of the EU MDR (and the MDD); specifically, that manufacturers have the liberty to devise and employ alternative conformity solutions if such solutions fulfill GSPR requirements.

Again, this remains the case even though EU MDR Annex VII requires NBs to "give consideration" to guidelines and best practices.  I suggest that "giving consideration" be interpreted in accordance with my preceding explanation above.  In other words, I advise that "giving consideration" does not mean mandate; indeed, such an approach would run contrary to longstanding European legislative and other precedent holding that neither standards nor guidelines are legally binding (unless a particular standard or guideline is specifically demanded by a legislation).  In fact, MDCG 2021-5 applies a similar permutation of this principle even in the context of the almighty SOTA and GSPR #1, reminding us that giving account of SOTA does not mean SOTA is mandated.

By similar reasoning I also advise that the provisions of EU MDR Articles 105 and 106 defining the roles of the MDCG, including its participation in the development of guidelines, do not undo the aforementioned principles and fundamentals regarding the basic intentions for, and limitations of, standards and guidelines.

Manufacturers, as the penultimate experts on the development of their devices, need to retain their right to devise and apply GSPR conformity assessment solutions appropriate for the manufacturer's devices.  Such solutions might be based on conformity with a standard or guideline, or they might not.

Dear all,

Probably I'm wrong, but I'm not so sure that this MDCG guidelines are "only guidelines". 

For my understanding the Auditor asked for what is stated in MDR. I don't consider this request "poor" but  absolutely appropriate  "clarify where the evidence for using and considering MDCG guidelines can be found "

ANNEX VII REQUIREMENTS TO BE MET BY NOTIFIED BODIES, in article related to "Conformity assessment activities" it is clearly stated: the notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.

The notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.

For Clinical evaluation assessment in particular, it is stated that: These procedures referred to in the first paragraph shall take into consideration available CS, guidance and best practice documents.

Also the Article 105 of MDR list of all task of the MDCG.

In particular (c), (d) and (e) are interesting in device development. I list them below.

(c)        to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;

(d)        to contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation (EU) 2017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex I to this Regulation;

(e)        to contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;

In article 106 it is also stated: The clinical evaluation guidance referred to in point (c) of paragraph 10 shall be published following consultation with the MDCG.

paragraph 10 (c) : (c) to develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;

It would probably be advisable to seek the advice of some lawyer.

Best regards,

K

Thanks, Vidya for the four additional questions.  A lot to unpack there; forgive me for the lengthy (yet still abbreviated) answer.  For liability reasons, a full response would need to happen under the covering of a consulting agreement and via direct communications, as a forum venue leaves ample opportunity for misunderstandings.  I'll do my best to give a general answer that I hope will contain some useful nuggets.

But before generally responding to the four questions, let me for the record first add to my prior narratives by stating that my firm's general policy is to encourage clients to always make a good faith effort to conform with applicable guidelines such as the MDCG guidelines (which in the case of clinical evaluation and PMCF, also point us back to certain aspects of MEDDEVs).  Reinventing wheels is in my opinion to be avoided wherever possible and appropriate.  And like Uwe wisely mentioned, when organizations apply such guidelines, NBs tend to give a something like a presumption of conformity similar to the way they respond to harmonized standards.  I've said before in the Forum that, even though we may indeed have legal and technical grounds for alternative approaches, it is true that the path of least resistance has definite benefits, often being less burdensome in the end then fighting an agency.  But when push comes to shove, and especially in a scenario where GSPR conformity can legitimately be achieved via a route other than the paradigm(s) recommended in a guideline, then it is, for multiple reasons, imperative that manufacturers retain the right to employ customized solutions.  That principle is paramount in the MDD and EU MDR and must not be dismissed by any NB.

My responses to the four questions:

1) In the context of clinical evaluation, let me first say that my firm's general processes for clinical evaluation are based on the aforesaid MEDDEVs as adapted for the EU MDR, and on related MDCG guidelines.  But if an NB says, "Would you please provide" evidence of conformity to non-binding guidance documents, then I would be cautiously optimistic that the NB realizes guidelines are not mandatory.  And if an organization finds itself in a scenario where conformity with those guidelines isn't appropriate, then I reiterate what I said before:  Specifically, an NB's conclusions about clinical evidence are, by legislation, to be focused not on guideline conformity, but instead on GSPR-related focal points like whether the clinical evidence sufficiently addresses the benefit-risk determination, whether the evidence is consistent with the intended purpose and medical indication or indications and sufficiently address device safety and performance, and whether the PMCF plan (if any) is adequate.

Accordingly, if an NB lodges an objectionable request/demand for conformity with non-binding clinical evaluation guidelines, then an organization's response needs to be primarily focused on demonstrating that the clinical evidence sufficiently addresses the applicable GSPR, and needs to do this in terms of the aforesaid NB clinical evidence assessment focal points.  Ultimately, in responding to such an NB request, an organization needs to state its rebutting position respectfully and scientifically, and then ultimately declare that the organization believes that its clinical evidence sufficiently address the applicable GSPRs and NB focal points.

If a scientifically reasonable case can in fact legitimately be made, and is made, then that can have several positive effects: It tends to relieve the NB's aforesaid liability; it makes it easier for the NB to accept the alternative route; and it also puts the onus back onto the NB to scientifically lodge a rebutting position.  That final effect is important; indeed, it's easy for an NB to cite an organization for not following a guideline or standard (and NBs know that many organizations readily capitulate), but it's not so easy for the NB to scientifically invalidate the organization's reasonable scientific rebuttal.  Once an organization makes a scientifically reasonable rebuttal, I've found that it often settles the issue.

As an aside, my experience has been that NB assessors (and even FDA inspectors) often want to help and offer alternative suggestions.  But remember that they can't do that without violating the code of ethics.  They are only allowed to state the apparent nonconformity, and without consulting or giving overt hints.  When I do my clients' internal audits in a consulting capacity where I have slightly more liberty to collaborate toward the greater goal of improvement and public health, I remind my clients, "…Listen, I have to write my findings a certain way within regimented boundaries that often make it seem like I'm demanding a certain 'inside the box' solution.  But that's not the intent of the finding; remember that I'm always open to hearing alternative solutions…"  I've found that this same dynamic often (but of course not always) exists with agency auditors.  Accordingly, when I'm in the auditee role, and if an outside-the-box solution is needed, then I be sure to lodge it and see the auditor's reaction before reaching conclusions about the apparent unreasonableness of the auditor.  If an assessor is in fact unreasonable, then I've repeatedly lobbied and appealed successfully in the past (I'll talk briefly about that below in question 4).

2) As noted in my prior post, the NBs are obligated by the EU MDR to "take into consideration" guidance and best practice documents.  MDCG 2019-6 gives a hint that this means that NBs are "encouraged to apply these guidance documents" (again revealing the non-binding nature of guidelines) during conformity assessments.  A myriad of examples show NBs doing this, such as when an NB requests (or inappropriately demands) conformity with MDCG or MEDDEV guidelines.

3) "…If NB cannot raise questions asking demonstration of compliance to MDCG per legal requirements…":  I would say that the NBs can raise questions about compliance with guidelines, and are legislatively allowed to do so as part of taking the guidelines "into consideration" under EU MDR provisions like Annex VII.1.6.2.  NBs can ask such questions, but NBs aren't allowed to lodge nonconformities about guideline conformity.  Remember that a big part of the game is NBs asserting the guidelines in hopes that the auditee has already complied, or will easily agree to comply (and in reality, that is often the easiest for everyone as noted before).

"…I'm assuming we can't respond using MDCG as basis, is that correct?" I would say that's actually incorrect.  Although this thread has a lot of posturing, huffing, and puffing about pushing back against potential NB overreach, don't let those contingency narratives and tactics give you the wrong idea.  As regulated entities, we are absolutely and intrinsically encouraged to apply MDCG guidelines since all MDCG-endorsed guidance documents do in fact reflect "the interpretation of the EU law jointly agreed by the authorities which are in charge of interpreting and applying the EU law."

4) There is indeed an appeals process that can be pursued in the event an organization can't come to terms with the NB through the regular channels.  I personally consider this type of approach to be a last resort, but have leveraged parts of it successfully before.  Note that the appeals process is generally governed by the standards that govern the NB (e.g., the EN ISO/IEC 17021 series).  I would actually say the appeals process starts by default in all conformity assessments by way of the fact that an auditor's findings and the auditee's response are subject to independent review by someone else within the NB.  That is a first opportunity for appeal that is already baked into the regular process.  Thereafter where needed, the next step is usually filing a formal complaint with the NB via its internal complaint process (see the NB contract and other NB procedures for a particular NB's complaint process).  If that doesn't resolve the issue, then a complaint can be filed with the authority that designated the notified body.  These appeal steps can take months or longer to play out, but are nonetheless appropriate in some cases.  And don't forget that in the midst of all this for the context of clinical evaluation of class III implantables (and certain other devices), the NB's clinical evaluation assessment report and the manufacturer's CER and PMCF documents are forwarded to the Commission and in turn to the Article 106 relevant expert panel for its opinion about the sufficiency of the level of clinical evidence.  So that intrinsic class III implantable clinical evaluation review mechanism also may provide an opportunity for appeal.  But as I mentioned above, I advise to only use an appeals process as a last resort.  In most scenarios, I believe that NBs prefer to avoid a formal appeals process.

Hope this helps!

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Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2021 by ComplianceAcuity, Inc. All rights reserved.

Original Message:
Sent: 15-Jun-2021 11:02
From: Vidya Jayaraman
Subject: NB requesting evidence MDCG documents are used as SOTA in device development

Appreciate your detailed, well-crafted response as always, Kevin. I have a few follow up questions:

1) What do you think of this Q from the NB - "Would you please provide a CER that is in full compliance with the MDR, MEDDEV 2.7/1 rev.4, MEDDEV 2.12/2 rev.2, and all relevant MDCG guidance's including MDCG 2020-6"
other than MDR, everything else is not legally binding, as we all know...They have made reference to MDCG 2020 in several other questions. For instance, "As this is not considered sufficient clinical evidence per MDCG 2020-6 section 5"

2) When you say guidance should only be "considered" - could you provide examples?

3) If NB cannot raise questions asking demonstration of compliance to MDCG per legal requirements, I'm assuming we can't respond using MDCG as basis, is that correct? For instance, use MDCG definition of WET as basis for sufficiency of clinical evidence.

4) Other than politely pointing out to NB that some of their asks are unreasonable (not saying they are in our case, just a hypothetical), is there any other way to appeal their decision like the FDA appeal process?

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Vidya
USA

Original Message:
Sent: 14-Jun-2021 18:26
From: Kevin Randall
Subject: NB requesting evidence MDCG documents are used as SOTA in device development

Hi Vidya,

I can't definitively address any particular scenario without full insights about the background facts and data.  But let me first reiterate that it is MDCG 2019-6 (rather than my own interpretation) that states that "Non-conformities will not be raised against standards or guidance but need to be phrased against legal requirements."  Indeed, without a corresponding ruling from the European Court of Justice (or perhaps even with a corresponding ruling), I know of no legal basis for phrasing a nonconformity against a standard or guidance.  Instead, nonconformities are to be phrased with respect to a legislative requirement (such as an applicable GSPR for example).

I don't believe class 3 implantable devices are automatically disqualified from being included in the WET category.  For example, EU MDR Article 61(8) acknowledges that certain implantable and class 3 devices may be found to be WET and thus eligible to be legally exempted from clinical investigations.  In other words, if class 3 implantable devices were automatically disqualified from being included in the WET category, then there would be no grounds for Article 61(8) to exist.

Further to my preceding explanations, and also to Annex IX section 5.1(a), an NB's conclusions about class III implantable device clinical evidence are to be focused on whether the clinical evidence sufficiently addresses the benefit-risk determination, the consistency of that evidence with the intended purpose and medical indication or indications, and the PMCF plan (if any).  As noted in my prior narratives, pursuant to EU MDR Annex VII, the NB is expected to "give consideration" to relevant guidelines, but shouldn't be citing guidelines in nonconformity narratives.  Instead, a nonconformity needs to be written with respect to a legislative requirement, such as an applicable GSPR.  A recipient's response to such a nonconformity (or proposed nonconformity) needs to be focused on demonstrating that the clinical evidence sufficiently addresses the applicable GSPR.  In any event, the recipient needs to have a scientifically-defensible basis explaining why its conformity solutions sufficiently address applicable GSPR.  This should be all stakeholders' fundamental focus rather than conformity with a guideline (unless the manufacturer has already declared that it applied the guideline as its conformity solution).

As an aside, remember that, for class III implantable devices not meeting MDCG 2019-6's WET definition, 2019-6 nonetheless accepts clinical evidence from studies with potential methodological flaws where data can still be quantified and acceptability justified.  So, if the clinical evidence measures up to this level of data quality, then there is grounds to declare conformity with MDCG 2019-6 even if the device fails that guideline's WET criteria.

Note also that the EU MDR definition of clinical evidence means clinical data and evaluation results that are of sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer.  This represents a potential wide spectrum of data, and certainly seems to give ample opportunity for all parties to rely on the clinical data from a legacy device.  If an NB is claiming that there is insufficient clinical evidence, then the NB must be able to fundamentally support a claim that the clinical evidence doesn't allow a qualified assessment of the device's safety and efficacy.  That seems to be a high bar, and certainly a subjective one, to be supported by the NB regarding a legacy device with extensive EU marketing tenure.

As another aside for an MDD-certified device being recertified under the EU MDR, be sure that the deliberations aren't being calibrated based on criteria for "equivalent devices".  This is because clinical data from an MDD-certified device being recertified under the EU MDR is not data from an "equivalent device"; instead such data are data from the same device.​

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Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2021 by ComplianceAcuity, Inc. All rights reserved.

Original Message:
Sent: 14-Jun-2021 16:33
From: Vidya Jayaraman
Subject: NB requesting evidence MDCG documents are used as SOTA in device development

Hi Kevin,

In response to your point that non conformities cannot be raised against a guidance - can review questions be raised claiming non-compliance with a guidance specifically MDCG 2020-6? The NB has commented that we have insufficient clinical evidence because our device is not a Well established device per criteria identified in MDCG 2020-6. The device is a class 3 implantable, wondering if that automatically disqualifies it from the WET category. Ironically, the MDR does not define WET and between MDCG and MDR, MDR takes precedence.

Of course under MDD, they did agree that the device was "well established" , the terminology did not exist until April 2020 when MDCG 2020-6 was released.

Thanks,
Vidya

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Vidya
USA

Original Message:
Sent: 14-Jun-2021 16:24
From: Kevin Randall
Subject: NB requesting evidence MDCG documents are used as SOTA in device development

Offline I received another comment that bears mentioning about how to record one's application of MDCG guidelines.  Specifically, regardless of whether the organization chooses a harmonized standard, an unharmonized standard, a guideline, a best practice, or some other conformity assessment solution, the organization needs to be sure to identify and record (and justify) such solution in the GSPR checklist.

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Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
Principal Consultant
Ridgway, CO
United States
© Copyright 2021 by ComplianceAcuity, Inc. All rights reserved.

Original Message:
Sent: 11-Jun-2021 12:06
From: Mark Mortellaro
Subject: NB requesting evidence MDCG documents are used as SOTA in device development

Hello Everyone,

Our Notified Body has asked us to "clarify where the evidence for using and considering MDCG guidelines can be found". They referenced GSPR #1  "...taking into account the generally acknowledged state of the art " with the request. We currently do not list MDCG documents in our Applicable Regulatory Standards (ARS) list because that list has been specific to standards that contain requirements. We do use MDCG documents and they are sometimes referenced within individual documents (e.g. our EUDAMED procedure), we just haven't added them to our ARS.

Adding MDCG documents to our ARS list seems a simple (one document only) solution but I would like to hear from the forum if listing MDCGs in the ARS list is typical. If there are other, simpler solutions that I can use to respond to the NB, please feel free to share them.

Thank you.

Mark



​​​

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Mark Mortellaro
Sr. Principal Regulatory Scientist
Senseonics
Clarksburg MD
United States
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