ISO 10993 (Biological Evaluation of Medical Devices) for Suppliers

[WisdomseekerSC]

We are a contract component manufacturer of specialty extruded polymeric materials (primarily tubing) for multiple industries world-wide. For our medical industry customers, we currently provide "medical grade" components that have passed USP Class VI testing. We don't always know what the end application is, but, we do extrude bioabsorbable materials for use in cardiovascular implants in direct contact with blood for > 30 days.

We are now transitioning to PFOA-free resins for some of our extrusion processes. As part of our Biological Evaluation Plan we will be retesting our materials .

We plan to survey our customer base to determine what testing they desire (USP Class VI or ISO 10993). We are also contemplating filing Master Access File (MAF) with FDA in the USA to provide our medical customers with additional support in filing 510(k) and PMA .

Question: As RA and QA professionals representing or consulting with Medical Device Manufacturers, what specific biocompatibility testing would you like to see from your Component Suppliers?

 

[Ronen E]

We are a contract component manufacturer of specialty extruded polymeric materials (primarily tubing) for multiple industries world-wide. For our medical industry customers, we currently provide "medical grade" components that have passed USP Class VI testing. We don't always know what the end application is, but, we do extrude bioabsorbable materials for use in cardiovascular implants in direct contact with blood for > 30 days.

We are now transitioning to PFOA-free resins for some of our extrusion processes. As part of our Biological Evaluation Plan we will be retesting our materials .

We plan to survey our customer base to determine what testing they desire (USP Class VI or ISO 10993). We are also contemplating filing Master Access File (MAF) with FDA in the USA to provide our medical customers with additional support in filing 510(k) and PMA .

Question: As RA and QA professionals representing or consulting with Medical Device Manufacturers, what specific biocompatibility testing would you like to see from your Component Suppliers?

Hi,

I would dare and say USP class VI is pretty much useless these days for a customer, from a regulatory submissions point of view. ISO 10993 is much better in that sense, though I wouldn't go too far in this direction either, because final product manufacturers are required to demonstrate biocompatibility IN THE FINAL STATE, and as such any material / component that is exposed to further processing after you supply it (e.g. sterilization) may have to be retested anyway (typically, integrated in the final product). In my view, the main benefit in ISO 10993 certified components is the relatively-high confidence level they provide that any such further testing will show compliance. As a start I would probably go for the 3 basic ISO 10993 tests.

A master file submitted to the FDA is always a treat for anyone working on a 510(k)!

Cheers,
Ronen.

 

[WisdomseekerSC]

Thank you for the prompt reply. Can you elaborate on which three ISO 10993 tests?

 

[MIREGMGR]

I agree with Ronen E.

As to which ISO 10993 tests, the current US FDA guidance is G95-1, unless FDA determines in a pre-submission conference with your customer that even more testing will be required.

I'm very surprised that your customers haven't already stated that to you, and that they think USP Class VI is still relevant to devices. That ended as of the adoption of G87-1, the predecessor to G95-1, in April 1987.

My understanding is that "for consideration" in the G95-1 tables should be read as "mandatory", because the latter is their operational intent but they don't want to fight the legal battles if they publish that specific word.

For a >30 day blood communicating implantable, it'll be eight tests, not three. It's not my area of expertise, but my understanding is that there might be other evaluations required for bioabsorbables.

 

[WisdomseekerSC]

Our purpose in ISO 10993 testing will be to provide confidence to our medical customers that our component parts are biocompatible. We only wish to SCREEN since the OEM will conduct the full gamut of testing based on the final finished device intended body contact and duration of exposure (since we are not privy most of the time). I think additional testing for the bioabsorable/resorbable materials may be in order. I just don't know which tests are the most appropriate for a general SCREEN to provide the comfort level needed for the value-added supplier tested materials we make. It may all revolve around the risk assessment and chemical characterization of the materials.

 

[Ronen E]

Our purpose in ISO 10993 testing will be to provide confidence to our medical customers that our component parts are biocompatible. We only wish to SCREEN since the OEM will conduct the full gamut of testing based on the final finished device intended body contact and duration of exposure (since we are not privy most of the time). I think additional testing for the bioabsorable/resorbable materials may be in order. I just don't know which tests are the most appropriate for a general SCREEN to provide the comfort level needed for the value-added supplier tested materials we make. It may all revolve around the risk assessment and chemical characterization of the materials.

Hi,

The 3 tests I referred to were Cytotoxicity, Sensitization & Irritation. By no means I said these are sufficient for any regulatory purpose (though in the greater sense - not for long-term implants - sometimes they are). I see this trio as a MINIMUM for the purpose of convincing customers that a certain product is in fact medical grade and has THE POTENTIAL of eventually qualifying by the book. Without them, I estimate most customers (if given a choice) would look for another, more supportive, source; that's because biocompatibility tests can take long and cost a lot, and most companies don't like to gamble (R&D is a gamble to an extent anyway ). Of course, if you have the resources and want to go further, more tests will bolster your position.

As I said before, in many cases your results (on your finished product, which would be a "raw material" for your customer) will not be usable as-is, because they don't necessarily represent the final device composition & state. I think it is not so much about providing your customers with hard results; it is more about providing perceived confidence.

Cheers,
Ronen.

PS I just noticed I accidentally missed a word in my previous post - I initially wrote "the 3 ISO 10993 tests", while I meant "the 3 basic ISO 10993 tests". Apologies.

 

[MIREGMGR]

I just don't know which tests are the most appropriate for a general SCREEN to provide the comfort level needed for the value-added supplier tested materials we make.

If I were a user of such materials and was considering your materials for the first time, without pre-existing test data of my own, I wouldn't want to make a development investment until I had pretty good confidence that those materials eventually would be able to pass the full set of tests. So, the screening data I'd want to see would be the hardest to pass of the full set of tests.

My understanding is that while the basic tests are considered to be easy as long as a material isn't acutely toxic, those tests that are only required for long term blood-communicating implantables are much harder to pass. Thus they'd make the best screen from the customer's viewpoint.

 

[WisdomseekerSC]

Wow...I hadn't thought of it that way. If material is reactive in the short term it would show up in a longer term study early on, if not then the study continues to evaluate the longer term effects. Although more costly, the longer term studies may provide more value for the dollar. It is typically a one time test unless material composition changes or significant change in the process is implemented that suggests a retest.

This discussion has been very helpful. Any recommendations for a good Biological Safety Testing Laboratory?

 

[Ronen E]

Wow...I hadn't thought of it that way. If material is reactive in the short term it would show up in a longer term study early on, if not then the study continues to evaluate the longer term effects. Although more costly, the longer term studies may provide more value for the dollar. It is typically a one time test unless material composition changes or significant change in the process is implemented that suggests a retest.

This discussion has been very helpful. Any recommendations for a good Biological Safety Testing Laboratory?

Check out NAMSA.

Good luck.