Regulatory Open Forum

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Stephanie:

While "State of the Art" can add real value, for say common or consumable devices, and assist in keeping "poor quality copies off the market" the concept seems to be pushed to breaking point as a mandatory process at every conceivable opportunity by the MDR. The concerns you raise are valid and I believe symptomatic of the MDR being written, and now interpreted by, eurocrats and lawyers with minimal understanding of how our innovation within the medical device industry works.

Personally, I am more concerned about requirement for "unethical" trials at the end of your post. Over the last few years, I have noticed the cutting back on rigorous laboratory testing programs as "well we have to do a clinical trial anyway". I take the principles behind the Declarations of Helsinki most seriously and expect to conduct every realistic laboratory test to be absolutely sure of any product before I allow its use on a human subject. Too often I visit hospitals only be show clinicians "trying out an idea" on a patient and to me the wording of the MDR and the universal PMCF requirements seems to encourage a quite deplorable laissez-faire approach to human experimentation.

My emphasis may be different but I agree with you and we need to limit the harm being done to the medical device industry and hence patients by the disproportionate and overly complex EU-MDR.

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Neil

Thanks a lot for your comments which I  agree with. 

Yes, the replacement of experimental modelling/ laboratory animals with humans is very troubling.

Since so many clinical investigations (CIs) are now required under MDR (even those where there are no unanswered questions, just regulatory requirement), one may assume that many unnecessary operations are being performed.

Luckily, according to reports of partners, some Ethic Committees/ IRBs have not granted permission to proceed with CI initiation. Hopefully, these same CIs did not  initiate in other countries in which ethical practice is questionable.  

In addition, since COVID, HCPs are scarce, they should be able to concentrate on helping patients and not manufacturing with the filling out of PMS/ PMCF surveys.  

At the core, State of Art (SoTA) MDR requirements are taking the decision-making away from the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️.

MDR SoTA Regulatory Requirement Assumption:

manufacturers/ NBs/ GAs can make this clinical decision if the medical device qualifies to be CE marked, based on SoTA argument (similar or better than SoTA). Are they qualified to decide which medical devices are considered to be SoTA or have the attributes to treat the condition/ disease? Ethical? In alignment with ISO 13485 (QM medical device standard)?

Why should a medical device have a similar or better benefit-risk ratio than the SoTA in order to receive a MDR CE mark?

- What about medical devices which address an unmet need which have a lower benefit-risk ratio than SoTA? Are we going to ignore the medical needs of specific patient groups in which other options do not exist?

-  What about "Standard-of-Care devices" having a very low cost? Do they all have to be replaced by more expensive new alternatives? What do medical facilities do in which the funding is limited or patients have a limited income or health institutions which rely on donations?

- What about innovative devices with no SoTA defined?  

- What about newly discovered medical conditions and diseases – with no SoTA established - should patients not be treated? 

- What about individuals with rare diseases/ conditions and unmet clinical needs;  their numbers are not sufficient to make SoTA conclusions?

Anyways, I will stop here...

Best Regards, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 22-Mar-2024 06:20
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie:

While "State of the Art" can add real value, for say common or consumable devices, and assist in keeping "poor quality copies off the market" the concept seems to be pushed to breaking point as a mandatory process at every conceivable opportunity by the MDR. The concerns you raise are valid and I believe symptomatic of the MDR being written, and now interpreted by, eurocrats and lawyers with minimal understanding of how our innovation within the medical device industry works.

Personally, I am more concerned about requirement for "unethical" trials at the end of your post. Over the last few years, I have noticed the cutting back on rigorous laboratory testing programs as "well we have to do a clinical trial anyway". I take the principles behind the Declarations of Helsinki most seriously and expect to conduct every realistic laboratory test to be absolutely sure of any product before I allow its use on a human subject. Too often I visit hospitals only be show clinicians "trying out an idea" on a patient and to me the wording of the MDR and the universal PMCF requirements seems to encourage a quite deplorable laissez-faire approach to human experimentation.

My emphasis may be different but I agree with you and we need to limit the harm being done to the medical device industry and hence patients by the disproportionate and overly complex EU-MDR.

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Hello Stephanie,

I agree that there could be cases where long term post market follow up is not necessary. The positive part is that it could be collected as part of real world data study and could help the company in developing additional products. It does increase the overall cost of the manufacturers and probably will make it unaffordable for some of them. 

I have this feeling that the overall intention of the MDR is to increase the investment in R&D since the pharma R&D has slowed down in the recent years. 

Have a great week,

Olga

Dear Neil

Thanks a lot for your comments which I  agree with. 

Yes, the replacement of experimental modelling/ laboratory animals with humans is very troubling.

Since so many clinical investigations (CIs) are now required under MDR (even those where there are no unanswered questions, just regulatory requirement), one may assume that many unnecessary operations are being performed.

Luckily, according to reports of partners, some Ethic Committees/ IRBs have not granted permission to proceed with CI initiation. Hopefully, these same CIs did not  initiate in other countries in which ethical practice is questionable.  

In addition, since COVID, HCPs are scarce, they should be able to concentrate on helping patients and not manufacturing with the filling out of PMS/ PMCF surveys.  

At the core, State of Art (SoTA) MDR requirements are taking the decision-making away from the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️.

MDR SoTA Regulatory Requirement Assumption:

manufacturers/ NBs/ GAs can make this clinical decision if the medical device qualifies to be CE marked, based on SoTA argument (similar or better than SoTA). Are they qualified to decide which medical devices are considered to be SoTA or have the attributes to treat the condition/ disease? Ethical? In alignment with ISO 13485 (QM medical device standard)?

Why should a medical device have a similar or better benefit-risk ratio than the SoTA in order to receive a MDR CE mark?

- What about medical devices which address an unmet need which have a lower benefit-risk ratio than SoTA? Are we going to ignore the medical needs of specific patient groups in which other options do not exist?

-  What about "Standard-of-Care devices" having a very low cost? Do they all have to be replaced by more expensive new alternatives? What do medical facilities do in which the funding is limited or patients have a limited income or health institutions which rely on donations?

- What about innovative devices with no SoTA defined?  

- What about newly discovered medical conditions and diseases – with no SoTA established - should patients not be treated? 

- What about individuals with rare diseases/ conditions and unmet clinical needs;  their numbers are not sufficient to make SoTA conclusions?

Anyways, I will stop here...

Best Regards, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 22-Mar-2024 06:20
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie:

While "State of the Art" can add real value, for say common or consumable devices, and assist in keeping "poor quality copies off the market" the concept seems to be pushed to breaking point as a mandatory process at every conceivable opportunity by the MDR. The concerns you raise are valid and I believe symptomatic of the MDR being written, and now interpreted by, eurocrats and lawyers with minimal understanding of how our innovation within the medical device industry works.

Personally, I am more concerned about requirement for "unethical" trials at the end of your post. Over the last few years, I have noticed the cutting back on rigorous laboratory testing programs as "well we have to do a clinical trial anyway". I take the principles behind the Declarations of Helsinki most seriously and expect to conduct every realistic laboratory test to be absolutely sure of any product before I allow its use on a human subject. Too often I visit hospitals only be show clinicians "trying out an idea" on a patient and to me the wording of the MDR and the universal PMCF requirements seems to encourage a quite deplorable laissez-faire approach to human experimentation.

My emphasis may be different but I agree with you and we need to limit the harm being done to the medical device industry and hence patients by the disproportionate and overly complex EU-MDR.

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Stephanie,

thank you for sharing the interpretations of some auditors/reviewers of NBs.  I would hope that those are not the norm.  

The term benchmark is not being used in the MDR.  Benchmarking to other medical devices in all aspects and expecting cutting edge technology thereof is not required. 

The MDR does not ask for SOTA it asked for "generally acknowledged state of the art" (GASOTA) and throughout the document it gives the tools what it means.  For example the compliance with harmonized Standards is GASOTA!

Changing the regulation will not happen in this reagards.  The MDR is clear on the requirements and if applied correctly it should not cause such problem.

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Some really good discussions here, and @Stephanie Grassmann I know we have been having similar discussions on your LinkedIn thread.

I agree with @Ludger Moeller's final line "The MDR is clear on the requirements and if applied correctly it should not cause such problem.". There is no requirement for benchmarking, being better than etc etc. This is about interpretation. If the reason to remove text from the MDR is because of inconsistent application by those carrying out the conformity assessment, then that inconsistency should be addressed rather than remove the requirement.

On the topic of the continuous PMCF....I hypothesise that some of the issue relates to the blurring of the lines between PMS and PMCF under the MDR compared to their pre-MDR usage, and some of it relates to NB's willingness to accept uncertainty and potential liability without the continued trawl for new clinical data.

------------------------------
Ed Ball
Manager, Intelligence & Innovation
United Kingdom

Original Message:
Sent: 09-Apr-2024 10:50
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

thank you for sharing the interpretations of some auditors/reviewers of NBs.  I would hope that those are not the norm.  

The term benchmark is not being used in the MDR.  Benchmarking to other medical devices in all aspects and expecting cutting edge technology thereof is not required. 

The MDR does not ask for SOTA it asked for "generally acknowledged state of the art" (GASOTA) and throughout the document it gives the tools what it means.  For example the compliance with harmonized Standards is GASOTA!

Changing the regulation will not happen in this reagards.  The MDR is clear on the requirements and if applied correctly it should not cause such problem.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 09-Apr-2024 07:53
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Ludger and Edward

To both of you, I value your opinions and thank you for your feedback. 

But to the following sentence, I am of a different opinion: "The MDR is clear on the requirements and if applied correctly it should not cause such problem."

If this was the case, then why are there so many different interpretations of the requirements by so many stakeholders?

Why do >2000 pages of MDCG guidances need to be issued?

No even the NBs agree on the requirements. 

"taking account of the generally acknowledged state of the art" with reference to effectiveness/ performance and safety mentioned in Annex I points 1, 4 is one example of many in which the NBs do not agree on how this should be addressed. 

Then there is the ongoing discussion, intended use = intended purpose as in the MDCG. However, our interpretation of MDR Article 2 intended purpose definition is that these two are not equal.  

Another example is the requirement of clinical data. Recently asked by NB to provide clinical data on instruments to implants. Instruments are available >20 years, standard of care devices and provide an indirect clinical benefit. At least the NB reviewer could be convinced that his requested clinical investigation on strictly the instruments does not need to be conducted. Nevertheless, he requested literature searches strictly on the instruments to find clinical data. 

List goes on ....

Best Regards,

Stephanie

Some really good discussions here, and @Stephanie Grassmann I know we have been having similar discussions on your LinkedIn thread.

I agree with @Ludger Moeller's final line "The MDR is clear on the requirements and if applied correctly it should not cause such problem.". There is no requirement for benchmarking, being better than etc etc. This is about interpretation. If the reason to remove text from the MDR is because of inconsistent application by those carrying out the conformity assessment, then that inconsistency should be addressed rather than remove the requirement.

On the topic of the continuous PMCF....I hypothesise that some of the issue relates to the blurring of the lines between PMS and PMCF under the MDR compared to their pre-MDR usage, and some of it relates to NB's willingness to accept uncertainty and potential liability without the continued trawl for new clinical data.

Dear Stephanie,

thank you for sharing the interpretations of some auditors/reviewers of NBs.  I would hope that those are not the norm.  

The term benchmark is not being used in the MDR.  Benchmarking to other medical devices in all aspects and expecting cutting edge technology thereof is not required. 

The MDR does not ask for SOTA it asked for "generally acknowledged state of the art" (GASOTA) and throughout the document it gives the tools what it means.  For example the compliance with harmonized Standards is GASOTA!

Changing the regulation will not happen in this reagards.  The MDR is clear on the requirements and if applied correctly it should not cause such problem.

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Stephanie,

Thank you for sharing your insights.

Your observations are quite intriguing. Just reading them makes my stomach turn. It seems like some individuals are out of touch. It is up to the community to address these issues.

I remember an inspection I observed many years ago. The medical device in question was a movable chair with a hole and a collection unit below it. When the inspector requested clinical data, I humorously suggested, "Please, take a seat, and you'll see that it works." 

In terms of regulatory professionals, there are three distinct types:

1. Pre-MDD professionals: They often propose the best solutions, although with some difficulties. The primary objective is pragmatism Unfortunately, this first type is now retired or is heading for retirements. 

2. MDD professionals: They faced frustration due to the previous weak surveillance system and a general lack of understanding of the directive. E.g. if a Post-Market Surveillance (PMS) was implemented the auditor still looked only at complaint handling. If it was a value for the client as it should be then it was not a problem.
These professionals managed to implement the regulations effectively and embraced the requirements. Additional surveillance measures introduced after the scandals resolved most of the issues. The sudden increase in observations by auditors hinted at the changing times (e.g. an auditor coming for several years leaving a company without any comments suddenly had observations in the double digits).  Those were then the beginning of the good times for consultants. And then the early signs of overreaction occurred, such as the unfortunate MEDEV deadline for clinical evaluations.

3. The influx of new professionals into the industry presents significant challenges. It's not their fault; rather, it seems there's total loss of pragmatism. Nonetheless, despite limited resources, many inexperienced individuals are striving to do their best. Let's address these challenges head-on.

One consequence is that the resume of the auditor must to be taken into consideration.   

I appreciate the example you provided regarding clinical studies of surgical Instruments. They should still be class I even though indicated for implants.  It's a perfect illustration for Article 61.10. I believe they are typically covered by standards, and if not, their performance can be demonstrated through bench testing. Certainly, they were used along the clinical studies for the implant.

Just imagine a randomized, double-blinded trial for a scalpel. Good luck with that.

All the best to you with your endeavors

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 12-Apr-2024 03:05
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Ludger and Edward

To both of you, I value your opinions and thank you for your feedback. 

But to the following sentence, I am of a different opinion: "The MDR is clear on the requirements and if applied correctly it should not cause such problem."

If this was the case, then why are there so many different interpretations of the requirements by so many stakeholders?

Why do >2000 pages of MDCG guidances need to be issued?

No even the NBs agree on the requirements. 

"taking account of the generally acknowledged state of the art" with reference to effectiveness/ performance and safety mentioned in Annex I points 1, 4 is one example of many in which the NBs do not agree on how this should be addressed. 

Then there is the ongoing discussion, intended use = intended purpose as in the MDCG. However, our interpretation of MDR Article 2 intended purpose definition is that these two are not equal.  

Another example is the requirement of clinical data. Recently asked by NB to provide clinical data on instruments to implants. Instruments are available >20 years, standard of care devices and provide an indirect clinical benefit. At least the NB reviewer could be convinced that his requested clinical investigation on strictly the instruments does not need to be conducted. Nevertheless, he requested literature searches strictly on the instruments to find clinical data. 

List goes on ....

Best Regards,

Stephanie

Some really good discussions here, and @Stephanie Grassmann I know we have been having similar discussions on your LinkedIn thread.

I agree with @Ludger Moeller's final line "The MDR is clear on the requirements and if applied correctly it should not cause such problem.". There is no requirement for benchmarking, being better than etc etc. This is about interpretation. If the reason to remove text from the MDR is because of inconsistent application by those carrying out the conformity assessment, then that inconsistency should be addressed rather than remove the requirement.

On the topic of the continuous PMCF....I hypothesise that some of the issue relates to the blurring of the lines between PMS and PMCF under the MDR compared to their pre-MDR usage, and some of it relates to NB's willingness to accept uncertainty and potential liability without the continued trawl for new clinical data.

Dear Stephanie,

thank you for sharing the interpretations of some auditors/reviewers of NBs.  I would hope that those are not the norm.  

The term benchmark is not being used in the MDR.  Benchmarking to other medical devices in all aspects and expecting cutting edge technology thereof is not required. 

The MDR does not ask for SOTA it asked for "generally acknowledged state of the art" (GASOTA) and throughout the document it gives the tools what it means.  For example the compliance with harmonized Standards is GASOTA!

Changing the regulation will not happen in this reagards.  The MDR is clear on the requirements and if applied correctly it should not cause such problem.

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

------------------------------
Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
------------------------------

Dear Ludger and Edward

To both of you, I value your opinions and thank you for your feedback. 

But to the following sentence, I am of a different opinion: "The MDR is clear on the requirements and if applied correctly it should not cause such problem."

If this was the case, then why are there so many different interpretations of the requirements by so many stakeholders?

Why do >2000 pages of MDCG guidances need to be issued?

No even the NBs agree on the requirements. 

"taking account of the generally acknowledged state of the art" with reference to effectiveness/ performance and safety mentioned in Annex I points 1, 4 is one example of many in which the NBs do not agree on how this should be addressed. 

Then there is the ongoing discussion, intended use = intended purpose as in the MDCG. However, our interpretation of MDR Article 2 intended purpose definition is that these two are not equal. From one NB, I received different definitions of the intended purpose.  

Another example is the requirement of clinical data. Recently asked by NB to provide clinical data on instruments to implants. Instruments are available >20 years, standard of care devices and provide an indirect clinical benefit. At least the NB reviewer could be convinced that his requested clinical investigation on strictly the instruments does not need to be conducted. Nevertheless, he requested literature searches strictly on the instruments to find clinical data. 

List goes on ....

Let us not forget, that there are also multiple official definitions of "State of the Art" which do not aid in the interpretation of SoTA requirements of the MDR. 

EN ISO 14971: 2019, Section 3.28

"..developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology and experience. 

Note to entry: The state of the art embodies what is currently and generally accepted as good practice in technology and medicine. The state of the art does not necessarily imply the most technologically advanced solution. The state of the art described here is sometimes referred to as the 'generally acknowledged state of the art"

or

MEDDEV 2.7/1 Revision 4, Section 8.2

"includes applicable standards and guidance documents, data that relate to benchmark devices, other devices, critical components and medical alternatives or to the specific medical conditions and patient populations intended to be managed with the device."

or IMDRF/GRRP WG/N47 2018 Section 3.43 or ......

Best Regards,

Stephanie

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 10-Apr-2024 10:57
From: Edward Ball
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Some really good discussions here, and @Stephanie Grassmann I know we have been having similar discussions on your LinkedIn thread.

I agree with @Ludger Moeller's final line "The MDR is clear on the requirements and if applied correctly it should not cause such problem.". There is no requirement for benchmarking, being better than etc etc. This is about interpretation. If the reason to remove text from the MDR is because of inconsistent application by those carrying out the conformity assessment, then that inconsistency should be addressed rather than remove the requirement.

On the topic of the continuous PMCF....I hypothesise that some of the issue relates to the blurring of the lines between PMS and PMCF under the MDR compared to their pre-MDR usage, and some of it relates to NB's willingness to accept uncertainty and potential liability without the continued trawl for new clinical data.

------------------------------
Ed Ball
Manager, Intelligence & Innovation
United Kingdom

Original Message:
Sent: 09-Apr-2024 10:50
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

thank you for sharing the interpretations of some auditors/reviewers of NBs.  I would hope that those are not the norm.  

The term benchmark is not being used in the MDR.  Benchmarking to other medical devices in all aspects and expecting cutting edge technology thereof is not required. 

The MDR does not ask for SOTA it asked for "generally acknowledged state of the art" (GASOTA) and throughout the document it gives the tools what it means.  For example the compliance with harmonized Standards is GASOTA!

Changing the regulation will not happen in this reagards.  The MDR is clear on the requirements and if applied correctly it should not cause such problem.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 09-Apr-2024 07:53
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Ludger

I really appreciate your comments, recommendations and ideas.

Based on feedback at the IMDRF in Washington DC, they are considering revisions; consequently, possible revisions are being proposed here in this post.

Yes, you are correct with the overinterpretation of the MDR.

The many interpretations of the MDR has not made the process of MDR CE marking efficient.

There are also >2000 pages of MDCG guidances with some statements which deviate from the MDR text.  

Involved in Technical Files, Clinical Investigations and Clinical Evaluations for almost 20 years, I am hoping and praying that there will be revisions to the MDR.

Here is one example of many, which I and others are confronted with:

·      NB state of the art (SoTA) interpretation may prevent a MDD CE marked Class IIa from being MDR CE marked.

·      Subject device with > 4 comparative clinical investigations (setup, reporting, etc. based on SoTA clinical practice).

·      Next NB round costs 30,000 USD (a small portion of what has already been paid in NB fees)

·      Market release in USA took <3 months at a fraction of the cost.

NB wants the benchmark values for outcomes of each device type of the generic group (with same intended use).

·      Some are standard of care devices in which benchmark values have never been published.

·      All systematic reviews in this medical area state no benchmark values available. NB was informed and received literature summary with the copied statement of each systematic review publication stating that no benchmarks for outcomes are available. Each publication explained the multiple reasons why outcome benchmarks are not available. 

Different reasons may lead to no SoTA outcomes/ benchmarks being defined i.e. outcome definitions not harmonized, test setups not standardized, etc.

Innovative devices or new medical device areas face the same struggle to address the NB interpretation of SoTA (Annex I GSPR, point 1,4). 

More than one company/ group recommended to take just values from 1 publication and paste them into the Technical File to fulfill the NB Checklist. This is going on.

Are we not defeating the prime objective?

Are individuals with clinical training and clinical practice not better qualified to assess if the clinical performance and effectiveness of medical devices (with a direct clinical benefit) are state of the art?

Is the safety profile not the most important?

Does every device really need to be state of the art?

In consideration of EU4Health and/or public health care systems is medical access not being restricted with the SoTA requirement for every medical device?

Proposal:

Subject medical device has to have similar safety to those on the market for the same patient group (similar patient characteristics not limited to clinical indications) and be effective and perform according to its stated intended purpose and clinical benefits (stated in informational materials).

Unfortunately, not every company has the financial means to bring these issues to the courts.

As a consultant, I am waving the red flag – not yet the white flag.

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 05-Apr-2024 06:56
From: Ludger Moeller
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Stephanie,

Thank you for bringing this up. It seems to me that there is an overinterpretation of the MDR. The definition of "SOTA" according to the Cambridge Dictionary is: "very modern and using the most recent ideas and methods." However, this is not what the MDR states. The MDR states: "taking into account the generally acknowledged state of the art" (GASOTA). There are also some other limitations given in section 1, which state: "They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety."

The overall explanation of different terms in relation to SOTA, GASOTA, or other similar related terms can be very tricky. There are different aspects in different industries, and it does have its meaning for any liability concerns. There are terms defined as well, which are used by the courts. The conclusion regarding how the term is used here, with its limitations, should be that a manufacturer is not allowed to place an inferior product on the market, and it does not need to be superior to products already on the market. And this is only in relation to the aspects listed.  

In most cases, that means compliance with the harmonized standards or CSs (Article 8 and 9, presumption of conformity etc.).  This is considered acceptable and common knowledge as well with NBs. The MDR makes it quite clear, what is required in terms of "generally acknowledged SOTA".

Here are the extremes: A product that is fully described in a harmonized standard does not need any additional Clinical Data nor PMCF. If a product is not fully covered by standard, then Common Specifications could be helpful. Those should be developed quickly, especially for low-risk class products if they are not fully covered by standards.

Examples of products which are partly covered by standards still may have sufficient standards for compliance. E.g., safety and performance standards. A good portion of electrical medical devices are covered by those standards. So, a Clinical Study or even any PMCF for such aspect would be unethical and declining a clinical study is fully acceptable by the MDR. Article 61.10 and the applicable MDCG make this clear. Other standards would reduce the need for any clinical data like, for example, Biocompatibility or Sterility, etc., to name a few. There is no need for any clinical study. Bench testing or, in some cases, lab validation testing will satisfy Annex I.  The clinical evaluation would outline all of those aspects.

So, a good portion of class IIa and a somewhat lesser portion of class IIb devices may not need any Clinical study or PMCF. Definitely, they do not need any PMS surveys. On a side note: In any case, no product needs surveys. Another overinterpretation based on the misinterpretation of some terms used in the MDR.  Nowhere is the term survey stated in the MDR.  There is simply no requirement as such stated in the MDR. I did check again for this outline.  The word survey is not used once.

For high-risk class products under the MDR (class IIb implantable or class III), clinical data are a must but only for the portions not covered by a standard or a CS. This should reduce the clinical testing to a bare minimum.

Most certainly, manufacturers and NBs should make use of the grandfathering options for legacy devices, which may also apply to new devices under Article 61 points 4, 5, and 6. If a notified body questions the clinical data of a legacy product, then it should ask itself what was done under the MDD, because in essence, the clinical data requirements have not changed. The feedback received from manufacture are that high number of deviations are written regarding the clincal files.  However, very often those deviations are based on administrative aspects and not the lack of data.  In order to avoid that a manufacturer may consider to put old data in a new format to get the notified body to agree. However, it would make sense to reserve that for new products and leave the legacy products alone in terms of clinical data, allowing the manufacturer to update the files with the upcoming PMCF.  There is no value in rewriting the same in a new format.  If the product was on the market under the MDD the clinical data should be sufficient or logically the NB did not do its job under the MDD.  

I understand the concern and I was amazed of the problems Annex XIV Part A is causing.  Thank you for bringing this up:
"...

This clause should be possible to answer quickly for most low-risk class medical devices. Crutches cannot be replaced by a drug. And the alternative for a hip replacement may as well be dire. Be careful. The delay for doing a hip replacement may be a question, but a manufacturer may define the specifications exactly when a hip replacement would be indicated, excluding any drugs. Any early replacement would be the choice of the patient and physician.

Indeed, the requirement is needed for products that compete with drugs, and the alternative should be looked at early on in the development phase of a device. I'd like to question whether drug companies have the same requirements in their regulations. If so, it should help the manufacturer to dig up those data.

One last comment on innovative devices: They are indeed SOTA and not GASOTA. Clinical data may be indicated even for low-risk devices. The data will then establish the GASOTA in the absence of any standards or CS. This should also be understood by the NB. However, indeed they may be afraid of the liability to move in this direction; then, indeed, we need a European FDA which limits the liability.  Not a good outlook but this is what seems to be requested now considering cost and timeliness with comparing it with the FDA which seems to  be currently on the other side of the pendulum.  

Stephanie, in writing this I have the feeling that I am not commenting specifically on the concern you raised specifically but rather outlining a different way of looking at the MDR to add to the overall discussion.  I have a very positive perspective regarding the written document but do not like the reading in between the lines, which is called interpretation by some to justify a requirement. NBs are prone to that due to strict surveillance and the initial strict "interpretation" bestowed upon them by authorities. (E.g. excusing themselves of not being allowed to consult - even though there is clear requirement in the MDR to explain the regulation).  Some, not all consultants have big ideas as well when implementing the requirements.  It seems that authorities are indeed the ones starting to back off now. Some of the readings in between the lines have been clarified by the courts, and it was good to see that at least the courts were sticking to the words written! In between the lines? There is only white paper between the lines! Certainly, only if you have printed on white paper.

------------------------------
Ludger Moeller
President, MDSS GmbH
l.moeller@mdssar.com

Original Message:
Sent: 04-Apr-2024 04:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear Neil

Thanks for your support here. 

Yes, the regulatory framework has to be more flexible for innovation and the AI revolution in Europe. 

We also have to focus more on the safety. With the state of the art requirement as given in the MDR Annex I General Safety and Performance Requirements, we have to realise the implications of these requirements - as interpreted by some/ NBs to mean that the subject device has to be comparable in benefit-risk to many existing existing therapies and devices and then requiring the outcome values of each in terms of performance/ effectiveness/ safety (separate costly analyses if values not in literature). 

How about patients with multiple co-morbidities which may be better served by safe device that is less effective or an individual at the end-of-life who wants to have Quality of Life provided by a standard care device (which may not be State of the Art)?

Medical device which is labelled as "State of the Art" also has an associated cost.

Regulatory authorities and NBs always shove the cost factor to the side. However, at the end of the day, financials do matter. Public healthcare systems can not afford that all medical devices are "State of the Art".

Manufacturers want to make profit. But if the CE mark costs 1/4 million in NB fees versus the 510(K) costing next to nothing in comparison and the time to regulatory release 18 months versus 3 months, the choice of market release location is clear. How many medical devices have to be sold to cover this cost? Yes, there are examples of this high CE mark cost in e.g. CORE-MD webinars (specifically the webinar at the end of 2023). 

The "Red Cross" mentality in the EU has to stop. 

Hoping and praying at we will get some good news at the EURO Convergence Meeting in Berlin!

------------------------------
Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 03-Apr-2024 06:59
From: Neil Armstrong
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Hi Stephanie:

From the addled recesses of my ossified memory, I remember a meeting with industry and the Deputy Raporteur about 2012 when we proposed something similar. A focus on the nature of the innovation (unfulfilled need, updated/safer technology/materiel, quality/reliability/consistency improvements, reduced cost) and a comparison to "state of art" like the FDA 510[k] to establish the baseline product/performance was no worse than those already on the market. Somewhere here we drifted into benefit-risk assessment and cardinal utility theory. Months and years past and the Commission redraft eventually got laid before the European Parliament (all reference to software had been deleted, revolutionary products had somehow acquired EMA oversight and our suggestion of a mid-upper three quartile benchmark "state-of-the-art" had mutated into a "cutting-edge" latest research type of requirement). There was to be another major re-draft and software got its own classification regulation eventually, but alas the idea of a focus on innovation had been replaced by the medical profession's preference for unnecessary double blind clinical trials. Ok, enough of recollections of opportunities lost in the tortuous process! Stephanie I agree with your approach, why not see if it can gain support. On the cusp of an AI revolution, we need new creative ideas about how to assess developments. It would make a great workshop for a RAPS meeting sometime!

Yours aye

Neil

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Neil Armstrong FRAPS
MeddiQuest
Peterborough UK
Waterford Ireland

Original Message:
Sent: 26-Mar-2024 02:57
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

If the State of the Art  (SoTA) requirements (addressing in particular MDR Annex I Art.1 and 4) are removed from #MDR  then what?

First the medical device regulation (MDR) should ask the manufacturer why the medical device should receive the MDR CE mark:

• Unmet medical needs
• Medical device/ therapy has additional benefit(s) in comparison to medical device/ therapy already on the market for this intended use. For instance, the surgical procedure time is cut in half.
•  Addresses a new medical area, a new disease/ condition found or a new diagnosis
•  Innovative device which does not bring higher residual risks or overall risk profile than another medical device/ therapy on the market
•  Standard of care medical device/ therapy (well established in medical area)
•  Addresses special needs i.e. bringing quality of life to those at the end of life
• Medical device/ therapy previously CE marked and since CE marking no new residual risks and/ or the medical device has not been found to have a higher risk profile than that which was declared at CE marking
• Medical device/ therapy is supported by professional medical association

-              Etc.

Based on the reasoning, the required process and regulatory requirements to CE marking (market access) would be defined. Consequently, the medical device regulation would be set up in a modular form with each module representing the reason for market access. Modular regulatorory design may shorten future revision in the future.

Yes, this proposal has similarities to the regulatory framework of the FDA in which different market access programs address different needs i.e. Breakthrough .. for unmet needs...etc.

In the EU, we need to focus on the patient and providing medical device/ therapy options to the physicians 🧑🏽‍⚕️ and HCPs 👩🏻‍⚕️👨🏿‍⚕️ to optimise patient care.

Best Regards,

Stephanie

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Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland

Original Message:
Sent: 21-Mar-2024 05:48
From: Stephanie Grassmann
Subject: "An indicative list and specification of parameters" derived from State of Art Literature - Cannot be addressed

Dear All

Any comments or recommendations to our dilemma with MDR "SoTA" requirement are very welcome. 

Kindly request any EU regulatory authorities to reach out to me privately. We need to keep these devices on the market.

Revisions are being considered for the MDR this year according to discussions/ presentations at IMDRF meeting.

https://www.imdrf.org/sites/default/files/2024-03/European%20Union.pdf

In order to proceed as quickly as possible to limit the damage, deletion of passages should be considered prior to revision of passages of the MDR as the first passage of amendment.

-> Revising the text, with so many stakeholders having a say, will take a lot of time, whereas, deletion of clauses may not.  

The following passage should be deleted to allow innovative devices or devices from innovative medical area to come to market is the following pertaining to Clinical Evaluation.

Unfortunate that the EC believes that innovative medical devices should be covered by another regulation, presently being written, rather than considering taking the detailed requirements out of the MDR.

"An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. "

This passage is preventing some MDD CE marked device to be MDR CE marked as well as other innovative devices and devices from innovative fields from being MDR CE marked.

How you may ask?

- For some medical devices, there is no State of the Art defined since the medical area is so new i.e. a new diagnosis or disease discovered.

- For other medical devices which are so innovative, the State of Art (SoTA) has not been established. For instance:

o   Recommended therapeutic pathway(s) has not yet been established for patients,

o   No standard testing/ verification/ validation methodologies are available and

o   100s of factors are known to affect the performance, effectiveness and safety but are not controlled or reported in studies.

o   Values for certain effectiveness/ performance parameters may vary from negative to plus.

- There are other cases in which the medical device has been established for such a long time that SoTA is not discussed and clinical investigations may originate pre-1970s with clinical study setups which do not allow cross study comparisons. Medical devices are considered SoTA and/or standard-of-care devices.

What does the notified body (NB) say to our concerns:

- Take values from a publication and claim these are SoTA values.

We have also proposed trigger values to NB to address indicative values but these were not accepted.

What do others do with this passage if they fall within the above 3 bullet points?

- Same as the recommendation of the NB.

- Others choose a non-relevant parameter in which there is some consistency.

Consequently, this MDR requirement forces manufacturers – having products falling into the bullets above – in some cases to misrepresent their product.

Another idea or suggestion how to address the SoTA requirements (i.e. "indicative values")?

MDR appears to put the SoTA at a higher level than performed clinical investigations.

In our case, comparative clinical investigations have been performed, however, this does not matter since the MDR requirement of "indicative list and specification of parameters" as well as others (which need to be derived from SoTA) cannot be met. 

MDR unethical?

If one considers the Declaration of Helsinki in terms of the clinical requirements of the MDR, then one realizes that some of the requirements may be considered unethical e.g. requiring the following:

-              On-going PMCF with no reason

-              Execution of clinical investigations for devices of low to medium risk which have a long clinical history in which there are no unanswered questions or issues; they have been established as SoTA or standard-of-care devices.

Clauses associated with the above bullet points above should also be deleted.

With ever increasing shortage in medical staff, medical professionals should be allowed to concentrate on their activities rather than having to take time to fill out surveys in order that manufacturers can fulfill the MDR PMCF requirement.

Truthfully, most surveys are probably filled out by assistants with little/ no knowledge about the device. And yes, this is going on. Data collected from PMCF surveys may be considered to inaccurately represent the device.

Detailed regulation requires subject matter experts with an in-depth knowledge in the field.

MDR is a clear example of a "too detailed" regulation in which the expertise was not sufficient as demonstrated by several of the MDR clauses. 

Looking forward to your comments and recommendations, 

Stephanie

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Stephanie Grassmann
Founder & Managing Director of MedTechXperts Ltd
Biberstein
Switzerland
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