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  • 1.  510(k) - Biocomp. Endpoints

    Posted 29-Jul-2021 03:41

    Dear RAPS network,

    We have a device that contacts the brain surface during surgeries. You can imagine it as a kind of flat surface electrode.

    It is classified as External Communicating, Tissue/Bone/Dentin, < 24h.

     

    During the 510(k) review process, the FDA gave following feedback: "Your device may have indirect contact with blood via cerebrospinal fluid. As a result, the recommended endpoints according to the 2016 biocompatibility guidance should include hemocompatibility."

    Depending on the indication the device may make contact to cerebrospinal fluid, but we do not understand why this should trigger hemocompatibility as additional endpoint.

    Does anyone have thoughts on this or made similar experiences?

     

    Kind regards,

    Michael



    ------------------------------
    Michael Hottner
    Köln
    Germany
    ------------------------------


  • 2.  RE: 510(k) - Biocomp. Endpoints

    Posted 29-Jul-2021 07:48
    Edited by Marina Daineko 29-Jul-2021 07:48
    Hello Michael,

    usually during Biological Evaluation the worst case is considered. As your device may make contact to cerebrospinal fluid, it shall be assessed as well to prevent any possible adverse effects. The FDA guidance for Use of ISO 10993-1 recommends as follows: 

    For devices having indirect contact with circulating blood (regardless of contact duration), we recommend that you consider only hemolysis testing, as complement activation and in vivo thrombogenicity testing are generally not needed for indirect blood-contacting devices. However, for novel materials not previously used in legally US-marketed devices with cardiac or vascular applications, or for devices intended to release     a chemical into the circulating blood, some in vitro assessment of thrombogenicity (e.g., the effect of extractables and leachables on platelets and the coagulation system) may also be needed for devices with indirect contact with blood.

    Hope this helps.

    Best regards,
    Marina

    ------------------------------
    Marina Daineko
    Newtown PA
    United States
    ------------------------------

    Original Message


  • 3.  RE: 510(k) - Biocomp. Endpoints

    Posted 29-Jul-2021 08:59

     

     

     

    Hi Michael,

     

    This request strikes me as exceedingly conservative, but let's think it through.  The presumed risk would be leaching of compounds from your device into CSF, followed by transfer of those compounds from CSF to the circulatory system.

     

    The risk of leaching into CSF is non-zero; however, given the short contact duration, it seems that any actual leached quantities are likely to be low.  You might consider identifying the possible compounds at the device surface that could come from manufacturing processes (e.g., processing aids, EtO residuals), and assessing the risk they could pose.  Such compounds would not require migration through the device materials and would therefore be more readily available for transfer into the CSF in the relatively short contact duration you described.  Constituents in the device materials would have a lower likelihood of leaching in less than 24 hours, but making definitive conclusions that such risks are negligible can be difficult.

     

    I would expect the second step to be greatly hindered by the blood-brain barrier, that prevents passage of many compounds from the bloodstream to the CSF; however, my sense is that function may not work quite the same in the reverse direction (note that I'm not an expert physiologist).  This page describes how some compounds pass from CSF to blood:

     

    https://www.ncbi.nlm.nih.gov/books/NBK27998/figure/A2338/?report=objectonly

     

    Though the risks of the second step are likely to also be non-zero, it seems to me that they are low--and the overall risk of meaningful harm in terms of adverse hemocompatibility is negligible.  You may wish to consult with a toxicologist (or pharmacologist) to consider whether these initial thoughts can be fleshed out enough to adequately address what seems to be mostly a theoretical risk.

     

    Hope that is some help.

     

    Best regards,

     

    Ted

     

    --

    Theodore (Ted) Heise, PHD, RAC

    Vice President Regulatory and Clinical Services

     

    MED Institute Inc.

    1330 Win Hentschel Blvd.

    West Lafayette, IN  47906-4149 USA

    765.463.1633 ext. 4444

    http://medinstitute.com

    theise@medinstitute.com

     

     

     




    Original Message


  • 4.  RE: 510(k) - Biocomp. Endpoints

    Posted 30-Jul-2021 07:13
    Marina & Ted,

    Thanks a lot for your really helpful feedback.

    I like to concept to evaluate and rationalize the potential toxicological risk supported by our E&L data.
    We work with a skilled toxicologicst who might be able help.

    Kind regards,
    Michael

    ------------------------------
    Michael Hottner
    Köln
    Germany
    ------------------------------

    Original Message


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