Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate. 

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect). 
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

Hi Anon.

You might choose to check the guidance that came out this morning on Select Updates to Biocompatibility of Certain Devices in Contact with Intact Skin.  Since it is so new and I only saw the notice in the Federal Register this morning I don't know if this will provide any insight or assistance but it might be a place to start.

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

The (draft) guidance is now available at : https://www.fda.gov/regulatory-information/search-fda-guidance-documents/select-updates-biocompatibility-certain-devices-contact-intact-skin . With kindest regards,

------------------------------
Ary Saaman
Director, Regulatory Affairs
Lausanne
Switzerland
------------------------------

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

This message was posted by a user wishing to remain anonymous

Hi all, 
I saw the draft guidance but unfortunately it does not really answer my question. No specific info on the cleaning process impact.
Any opinion on what the reviewer is expecting?
Thanks
Original Message:
Sent: 15-Oct-2020 09:23
From: Ary Saaman
Subject: cleaning impact on biocompatibility (skin contact only)

The (draft) guidance is now available at : https://www.fda.gov/regulatory-information/search-fda-guidance-documents/select-updates-biocompatibility-certain-devices-contact-intact-skin . With kindest regards,

------------------------------
Ary Saaman
Director, Regulatory Affairs
Lausanne
Switzerland

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

Hi 

I will say the proposed cleaning agent is compatible with cleaning surface and has no impact on material properties of its surface coatings. Based on this rationale there is no impact of cleaning on biocompatibility

------------------------------
Swapnil Jain
Regulatory Affairs Specialist
Best
Netherlands
------------------------------

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

This message was posted by a user wishing to remain anonymous

The new guidance, while good, appears to be for comment only write now, not for implementation.
Original Message:
Sent: 16-Oct-2020 02:44
From: Swapnil Jain
Subject: cleaning impact on biocompatibility (skin contact only)

Hi

I will say the proposed cleaning agent is compatible with cleaning surface and has no impact on material properties of its surface coatings. Based on this rationale there is no impact of cleaning on biocompatibility

------------------------------
Swapnil Jain
Regulatory Affairs Specialist
Best
Netherlands

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

Hi Anon,

The biological evaluation of any device must be performed on the finished product. That means that if you have different "variations" of the product you have to assess them all. If your product is used only in a certain way according to the IFU, you have to assess this procedure.
I understand the point of the assessor for the cleaned once or cleaned many times. In your IFU you have to dictate how many times the device can be reprocessed. This procedure has, of course be validated.
By saying assessing biocompatibility, does not necessarily means to perform biocomp studies.You can perform material and chemical characterization on your product and assess the material changes (such as surface properties), degradation products or leachables and prove that if you repeat the cleaning process as many times as you have validated, the physico/chemical properties of the device are not affected. Then you can perform the necessary biocomp studies on the finished product.

Have in mind that you ALWAYS have to start with material and chemical characterization. These information will reveal all the problems about your product. Biocomp studies can hide a lot of problems.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece
------------------------------

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

Hello,

Without knowing the type of device, materials, and the recommended cleaning agents it is hard to comment, though maybe the reviewer is looking for what has already been commented: ensuring the cleaning materials do not alter or change the skin contact material.  Also the number of times the device is used, re-used, cleaned in between use, needs to be considered.  For me it is not a matter of the number of times you have to performed biocompatibility testing for the device, the question more is maybe the overall life cycle of device, usage, and cleaning has not been fully described for the reviewer.  It seems maybe you could perform a risk assessment or as mentioned a biological evaluation report to describe the device, device usage, cleaning, and biocompatibility risks.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs
------------------------------

Original Message:
Sent: 20-Oct-2020 03:03
From: Spyros Drivelos
Subject: cleaning impact on biocompatibility (skin contact only)

Hi Anon,

The biological evaluation of any device must be performed on the finished product. That means that if you have different "variations" of the product you have to assess them all. If your product is used only in a certain way according to the IFU, you have to assess this procedure.
I understand the point of the assessor for the cleaned once or cleaned many times. In your IFU you have to dictate how many times the device can be reprocessed. This procedure has, of course be validated.
By saying assessing biocompatibility, does not necessarily means to perform biocomp studies.You can perform material and chemical characterization on your product and assess the material changes (such as surface properties), degradation products or leachables and prove that if you repeat the cleaning process as many times as you have validated, the physico/chemical properties of the device are not affected. Then you can perform the necessary biocomp studies on the finished product.

Have in mind that you ALWAYS have to start with material and chemical characterization. These information will reveal all the problems about your product. Biocomp studies can hide a lot of problems.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide

This message was posted by a user wishing to remain anonymous

Hi all,
thank you for your feedback.
Spyros, I agree with your comment. After further discussion, we reached the conclusion that we don't need to repeat biocompatibility testing but only analyze changes in the material properties. 
One possibility is what you said, i.e., a differential analysis of leachables at time 0 and after a number of cleaning cycles, representative of the life of the product. Another option that we have just found would be ASTM D543: https://www.astm.org/Standards/D543.htm which, as far as I read, includes provisions for reporting changes in weight, dimensions, appearance and strength properties due to chemical reagent.

Any thoughts on pros/cons of these two options?
Thanks again for anybody that can provide feedback.


Original Message:
Sent: 20-Oct-2020 04:44
From: Richard Vincins
Subject: cleaning impact on biocompatibility (skin contact only)

Hello,

Without knowing the type of device, materials, and the recommended cleaning agents it is hard to comment, though maybe the reviewer is looking for what has already been commented: ensuring the cleaning materials do not alter or change the skin contact material.  Also the number of times the device is used, re-used, cleaned in between use, needs to be considered.  For me it is not a matter of the number of times you have to performed biocompatibility testing for the device, the question more is maybe the overall life cycle of device, usage, and cleaning has not been fully described for the reviewer.  It seems maybe you could perform a risk assessment or as mentioned a biological evaluation report to describe the device, device usage, cleaning, and biocompatibility risks.

------------------------------
Richard Vincins RAC
Vice President Global Regulatory Affairs

Original Message:
Sent: 20-Oct-2020 03:03
From: Spyros Drivelos
Subject: cleaning impact on biocompatibility (skin contact only)

Hi Anon,

The biological evaluation of any device must be performed on the finished product. That means that if you have different "variations" of the product you have to assess them all. If your product is used only in a certain way according to the IFU, you have to assess this procedure.
I understand the point of the assessor for the cleaned once or cleaned many times. In your IFU you have to dictate how many times the device can be reprocessed. This procedure has, of course be validated.
By saying assessing biocompatibility, does not necessarily means to perform biocomp studies.You can perform material and chemical characterization on your product and assess the material changes (such as surface properties), degradation products or leachables and prove that if you repeat the cleaning process as many times as you have validated, the physico/chemical properties of the device are not affected. Then you can perform the necessary biocomp studies on the finished product.

Have in mind that you ALWAYS have to start with material and chemical characterization. These information will reveal all the problems about your product. Biocomp studies can hide a lot of problems.

------------------------------
Spyros Drivelos
Medical Devices Expert, RAC
Agia Paraskevi, Athens
Greece

Original Message:
Sent: 14-Oct-2020 12:14
From: Anonymous Member
Subject: cleaning impact on biocompatibility (skin contact only)

This message was posted by a user wishing to remain anonymous

Hi,
we have just had a presub meeting with the FDA and we are a little puzzled about one of the comments of the biocomp reviewer.
In the written feedback, they asked us "how we plan to assess the impact of cleaning on biocompatibility. If there are changes in
the material properties and/or surface coating due to the cleaning process, these changes can compromise the biocompatibility of a device."

Our response was that:
1) we will perform biocompatibility testing on the final device that has been cleaned according to IFU.
2) we will also assess if cleaning affects our superficial layers of the device, i.e., we will perform repeated cleaning and see if we visualize any cracks, loss of colors, etc. If the surface seems damaged, we will consider repeating the biocomp test with the scratched or damaged sample. If not, we will consider our original results adequate.

It seems that this did not satisfy the reviewer, which kept asking how we assess biocomp on a "not clean" device AND on "a device that has been cleaned many times".
It sounds to me like they are asking to repeating cyto, irritation, and sensitization three times (not cleaned, cleaned once, cleaned many times).
If you consider that we need to test 4 samples, this will result in 12 biocomp tests, for a device that is intact skin only and maximum prolonged exposure (if we consider the cumulative effect).
Does anybody have any suggestion on how to address this comment? Whether any type of rationale can be used to justify the impact of cleaning?
Also, I am not sure why we should consider the "not cleaned" case, if the device needs to be cleaned before use.
Thanks for any help you can provide