New 510k required for a material change?

[WAF64]

Hello everybody,
we're changing a connector in a blood contacting medical device.
The new component is in PC while the old one (510k cleared) was PVC.
The component supplier gave us enough biocompatibility documentation to support our decision not to repeat biocompatibility testing.
So, because we have decided not to conduct additional testing should we file a new 510k for this change?

Thank you for your help!

 

[Mark Meer]

Hmmm, that's a tough one given that it's blood-contacting.

What is the nature of the biocompatibility documentation given to you by the supplier?

Does it meet the applicable ISO 10993 requirements?
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080742.htm

Also, you'll want to be certain that the evidence they've supplied to you reflect the materials as they will be in the final device. If there is additional processing (e.g. molding, coloring, polishing...) involved between the materials as presented by their evidence, and that in the final device, this could mean you'll have to do some testing on the finished material.

 

[Ronen E]

Hello everybody,
we're changing a connector in a blood contacting medical device.
The new component is in PC while the old one (510k cleared) was PVC.
The component supplier gave us enough biocompatibility documentation to support our decision not to repeat biocompatibility testing.
So, because we have decided not to conduct additional testing should we file a new 510k for this change?

Thank you for your help!

Hi,

Most likely you need to submit a new (special) 510(k), and perhaps you also need to conduct biocompatibility testing on the new finished device.

Cheers,
Ronen.

 

[WAF64]

Thanks Mark and Ronen for your answers.
Actually the documentation received (complete test reports) meets and exceeds the ISO10993 series requirements for our intended use.
The component will be used as is, without further processing except for terminal ETO sterilization.

We already use PC in other portions of our device but unfortunately the formulation is not exactly the same. I really don't think that the overall device biocompatibility can be impacted by the slightly different material formulation of a single connector, also considering its widespread use in analogous applications.

On the other hand I'm aware that FDA may not accept the rationale behind our decision not to retest.

I will discuss this further with my R&D but if additional testing/510k is necessary I guess the result will be "solution b" which is technically worse but there's no material change...

 

[planB]

WAF64,


ISO 10993-1 requires to test the _final_ product (representative), which typically includes all manufacturing steps including terminal sterilization:

1) Would you have a rationale why sterilization has no adverse impact on your final product?
2) What means "slightly" different formulation? What is your quantitative justification that the original complete test report still applies?

You may satisfy FDA expectations by the following approach:

Since you mention a _complete_ test report at hand, you should be also in possession of material characterization and cytotoxicity data for the unsterilized product. You also mention a biocompatibility file for PC of "slightly" different formulation

1) Repeat your material characterization study (ie.e. lechables and/or extractables gained by using solvents of different polarity) according to ISO 10993-18 on your final product, i.e. the terminally sterilized connector with slightly changed material formulation

2) Repeat Repeat your cytotoxicity test according to ISO 10993-5 on your final product, i.e. the terminally sterilized connector with slightly changed material formulation

3) Compare these two results to the two existing material characterization and cytotoxicity test results provided by your supplier and the PC you already use: if your leachables /extractables profiles and cytotoxicity results are equivalent you will have the rationale at hand to conclude that your new connector is biocompatible without having to experimentally re-study all the other biological risks.

HTH,

Gerhard

 

[Ronen E]

What about EtO residuals?

 

[planB]

What about EtO residuals?

Ronen,


thanks for raising this point.


EtO residuals are usually considered - and reviewed during submissions - as part of the sterilization validation according to ISO 11135, though from a standards point of view ISO 10993-7 is part of the 10993 series. So usually EtO residuals are not part of a biocompatibility evaluation file.


Having said this, EtO residuals are evaluated as part of the sterilization validation of the device: either you demonstrate this by rationales (PVC, your former material, is in many cases a worst case for residuals, which might be also true for this device under discussion) or do dedicated new experimental residuals studies according to ISO10993-7 in case you do not have an already qualified worst-case representative for residuals at hand.


HTH,


Gerhard

 

[WAF64]

Thanks for your post Gerard, this makes sense to me.
We will evaluate the existing documentation to assess feasibility of this approach.

With this rationale at hand, do you believe a special 510k would still be required?

 

[planB]

With this rationale at hand, do you believe a special 510k would still be required?

Unfortunately, I am not a regulatory specialist, but you might be able to use this guidance to your advantage:


http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm#page16


and specifically this section:

C2.2.1 ...A 510(k) may not be needed if the manufacturer has satisfactory results from the testing indicated by ISO 10993-1 in its files for the material in question or if such results are available to the manufacturer, e.g., are available in the open published literature or have been provided to the 510(k) holder by the material supplier.

To my experience, FDA is open to informal discussion. So you could inquire with FDA presenting your case and your rationales why you consider your changes as being insignificant not warranting a submission. You could outline your rationales to FDA, why the existing data allows you to establish biocompatbility for the changed device and that you perform limited testing only to support your conclusion that you have already drawn from your existing data. In case FDA still wants to see a submission, the agaency will tell you.


HTH,

Gerhard

 

[Ronen E]

Unfortunately, I am not a regulatory specialist, but you might be able to use this guidance to your advantage:


http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm#page16


and specifically this section:


To my experience, FDA is open to informal discussion. So you could inquire with FDA presenting your case and your rationales why you consider your changes as being insignificant not warranting a submission. You could outline your rationales to FDA, why the existing data allows you to establish biocompatbility for the changed device and that you perform limited testing only to support your conclusion that you have already drawn from your existing data. In case FDA still wants to see a submission, the agaency will tell you.


HTH,

Gerhard

My guess is that FDA will ask for a new submission in which the additional biocompatibility data and any additional analysis / rationalisation are included. I don't think that FDA has another mechanism for reviewing such a compilation.

Cheers,
Ronen.