Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

Hello, 

Depending on the class and type of device, you may be able to claim equivalence to a competitor device without pushback from the Notified Body. 

If the device is class III or implantable and does not meet any of the cases in MDCG 2023-7, then you're correct, a clinical investigation is required. In terms of the strategy you've outlined, I have seen manufacturers take this approach. Although the timeline may be shortened, be aware that more resources will need to go into preparing your clinical documentation--the CER and PMCF will need to be created for the initial submission, then re-worked with an entirely different evaluation strategy once the clinical investigation is complete. 

Best,

------------------------------
Bethany Chung, PhD, RAC
Principal Consultant
MD, United States
------------------------------

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

There is only one way to claim that you have an equivalent device to a competitor device.  You must have a written agreement with you competitor in place that state that you have full excess to all technical documentation including the clinical evaluation report.

------------------------------
Armin Beck
CEO
SunTrixConsulting LLC
El Dorado Hills, CA
1-925-212-7683
armin.beck@suntrixmedical.com
------------------------------

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

Dear Anon

Please be aware that the equivalence definition under MDD is not the same as under MDR (see Annex XIV #3).

You will need full ongoing access to the Technical File of the equivalence device through a contract. The CER of equivalent device also has to have been performed according to the MDR and the manufacturer of the equivalent device has to deliver proof to the NB to this point. 

There are many other variables to consider on how to best move forward. Clinical investigations are very costly and take time, as we all realise. 

All the best,

Stephanie

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

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

Hello Anon,

As said before, this would highly depend on type of device, the novelty of device, classification, and intended purpose depending on the sufficient clinical evidence which would be needed.  Already if you state the device is a relatively new technology, the equivalency route might not be feasible even from the beginning.  Typically new applications, novel technology, or outside state of the art would find it difficult to claim equivalency under the EU MDR.  You have to prove through scientific methods your device is equivalent to another device.  Armin, I respectfully disagree with your statement - a contract is only needed for Class III and implants devices claiming equivalency (purposed for those manufacturers making changes to their own device).  However, even proving through scientific methods is not well accepted by Notified Body reviewers; it is definitely not the substantial equivalence method of US FDA.  Using equivalency in the European Union should be your last option.

If you have an ongoing clinical trial, and able to access the safety and performance data, it would be better to present what you have currently and then propose (negotiate) with Notified Body for a Post Market Clinical Follow-up (PMCF).  Unfortunately, the purpose and intent of PMCF has been lost by Notified Bodies as well, so this can also be a challenging pathway.  PMCF is intended if there was not sufficient safety or performance data, then continued proactive accumulation of clinical data could be made to support the safety and performance of a device.  These days under EU MDR, Notified Bodies apply this PMCF widely - or even as a requirement for any device.  A PMCF could be used exactly in your situation where you have some clinical data and to continue proactively gathering clinical data after the CE Mark is granted to ensure the clinical benefit versus risk, safety, and performance of the days is completely understood - especially in real world situations.

------------------------------
Richard Vincins ASQ-CQA, MTOPRA, RAC
Principal Strategy Consultant
NAMSA
------------------------------

Original Message:
Sent: 15-Apr-2024 03:00
From: Stephanie Grassmann
Subject: Equivalence and Clinical investigation

Dear Anon

Please be aware that the equivalence definition under MDD is not the same as under MDR (see Annex XIV #3).

You will need full ongoing access to the Technical File of the equivalence device through a contract. The CER of equivalent device also has to have been performed according to the MDR and the manufacturer of the equivalent device has to deliver proof to the NB to this point. 

There are many other variables to consider on how to best move forward. Clinical investigations are very costly and take time, as we all realise. 

All the best,

Stephanie

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

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

Dear Anon,

To be able to answer your question whether or not it is a better approach to wait for the submission until you have completed the clinical investigation or not, it is important to take the following into account:

You intend to have the clinical investigation ongoing at the moment of your submission. Will you do this study as a formal premarket study in the EU per article 62? If yes, how are you going to explain to the notified body if they do not accept the equivalence approach that you have completed an ongoing clinical investigation that you did not mention in your clinical evaluation. If you submit under article 82 in the EU, the data cannot be used for conformity assessment. 

Depending on the design of your clinical investigation, it may be possible to define a strategy in which you submit your clinical evaluation to the notified body based on for example short-term follow-up, while the study continues to collect longer-term follow-up data. 

In summary, if you do not include your clinical investigation in your initial submission, you want to have a great justification. If this is not the case, do not pursue the equiavalence route, but look at other options, such as submission with a limited clinical data set. 

------------------------------
Bianca Lutters PhD
Qserve Group (Netherlands)
Arnhem
Netherlands
------------------------------

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,

Hi Anon,

if I understand this correctly, then the question if you need a clinical investigation is already settled: you do. In this case I think the solution you propose would not work well for several reasons:

• For the submission with the equivalence pathway (that you already know will not work) you would need a clinicel evaluation plan and report with an extensive rational that you know you cannot sustain. That would mean a lot of effort on your side without any real use.
• For the answer to the foreseen challenge by the notified body you would then replace your clinical strategy with a new one and need to come up with an explanation why you did not do so in the first place (and why the clinical investigation you need is already running). That again generates effort without any real payback.
• The notified body will not be happy if they get the impression that you provided them with a submission you knew would not work, they invested time in reviewing this and providing feedback to you and you then suddenly come up with a complete new solution and fitting clinical trial you could have thought of in the first place.

Maybe I am overlooking something but that sounds like a waste of resources on both sides and not a good way of communicating with your notified body.

In my opinion the better solution would be to approach your notified body, be upfront about what you plan to do and see if you can find a solution where you fix a schedule according to the timelines of your clinical trial and optimize the review procedure alongside that. Maybe there is a possibility for the NB to start reviewing the already available documentation earlier, or to reserve a fixed timeslot for a quicker evaluation, or maybe find some other solution. This should be possible via the structured dialogue the EU proposed to nhance the efficiency and predictability of the conformity assessment process (see MDCG 2022-14).

Best regards, Christoph

------------------------------
Christoph Kiesselbach
Schrack & Partner
Reutlingen
Germany
------------------------------

Original Message:
Sent: 11-Apr-2024 20:29
From: Anonymous Member
Subject: Equivalence and Clinical investigation

This message was posted by a user wishing to remain anonymous

Hi all,

We will soon be having a prototype of a relatively new technology device, as such there is no previous generation device. We are in the process of doing a clinical investigation which would probably take time and may miss out on the expected launch timelines; hence wondering if for CE marking, we have the submission using the equivalence pathway (with the competitor device), which would be challenged by the notified body, however until such time we would have completed the CT to respond to the deficiency and thus save time for approval. Is this a better approach in terms of timelines for approval than waiting for the submission to happen post the clinical trial?

Thanks,