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Biocompatibility

  • 1.  Biocompatibility

    Posted 16-Jul-2019 04:13
    ​Hi All,

     Do we need to test again for the biocompatibility when we already chosen proven material for use in medical device. We are in the process of making active implantable medical devices and accessories. We have chosen material already proven biocompatibility. Please suggest do we need to go again for testing.

    Regards,
    Jayaram

    ------------------------------
    Jayaram Abimanyu
    Chennai
    India
    ------------------------------


  • 2.  RE: Biocompatibility

    Posted 17-Jul-2019 07:02
    While it may be a "proven medical material", that only imparts a likelihood that the material will successfully pass biocompatibility testing.  There is an issue of what type of processing or transformation (molding, extrusion) you perform to the material, as well as the potential effects of sterilization processes on the material.  Also, you fail to mention the duration of exposure as defined in ISO 10993, (i.e. limited, prolonged, implant) or the nature of body contact.  Authorities customarily want to see biocompatibility testing performed on the material as incorporate into the finished device as it will be presented for use.  You mentioned active implantables, so testing is pretty much a given.  The easiest path it to test rather than try to justify not testing, unless you are dealing with an iteration of your own device that is nearly identical with respect to the material in question.

    ------------------------------
    James Bonds J.D.
    Director Regulatory Affairs
    Atlanta GA
    United States
    ------------------------------

    Original Message


  • 3.  RE: Biocompatibility

    Posted 17-Jul-2019 09:07
    Hi James,
     
         One of the device used as an external accessory ​is to contact with tissue for prolonged periods, and the other device which is to be implanted is to contact tissue/bone permanently(>30days). Biocompatibility material is chosen for implant like titanium over mold with silicone. Similarly biocompatibility material is chosen for the external accessory as well. Do we need to test for the sake of regulatory requirement?.

    Regards,
    Jayaram

    ------------------------------
    Jayaram Abimanyu
    Chennai
    India
    ------------------------------

    Original Message


  • 4.  RE: Biocompatibility

    Posted 17-Jul-2019 18:44
    Edited by Julie Omohundro 17-Jul-2019 18:44
    You need to test for the sake of PATIENT SAFETY. 

    Various regulatory agencies may also require biocompatibilty data.

    ------------------------------
    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Mebane, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


  • 5.  RE: Biocompatibility

    Posted 18-Jul-2019 09:25

     

     

    Hi Jayaram,

     

    You've gotten some good input from others, most of which I agree with.  That said, there are a few additional points I'd like to make.

     

    Firstly, the paradigm of "biological evaluation = testing" is incorrect; the last two versions of 10993-1 have emphasized that the primary table (in Annex A) is a guide to the biological endpoints that need to be assessed (this is particularly prominent in the 2018 version).  Testing is of course one way the biological endpoints can be assessed, but they can also be addressed through appropriate rationale; for example, by demonstrating that prior data adequately represent performance of the proposed device, or that the available evidence provide no indication of a risk that warrants testing (e.g., carcinogenicity).

     

    Probably everyone recognizes that the number of biological endpoints to be assessed goes up with a long term implant, as compared to a device with limited or prolonged contact duration; however, it's also generally the case that it's more challenging to adequately support safety with justifications for all the applicable endpoints with a long term implant.

     

    Regarding your specific case, it *might* be possible to justify biocompatibility of the long term implant with an equivalence rationale.  This could be based on the silicone overmold material being the only device component with long term patient contact, and having a similar use case, surface area (and morphology), and material composition compared to an approved device.

     

    A justification for material equivalence would require evidence of equivalent composition (including processing); composition equivalence can potentially be adequately supported by supplier information, if very robust.  More likely, you would need chemical characterization data to support this--either demonstrating chemical equivalence, or coupled with toxicological risk assessment for those constituents having potential for greater exposure to the patient.

     

    The current ISO 10993-18;2005 has an annex on equivalence; this has been improved in the revision of this standard that is currently nearing completion.  The FDIS may be available to you now; it has been approved, and should publish by end of year.

     

    The limited information you provided about the prolonged contact component doesn't allow me to offer any advice on it; so too, the advice on the long term component is limited by the somewhat sparse details you gave.  I'd be happy to discuss in more detail, if you like--just contact me directly.

     

    Best regards,

     

    Ted

     

    --

    THEODORE HEISE, PHD, RAC

    Vice President Regulatory and Clinical Services

     

    MED Institute

    1330 Win Hentschel Blvd.

    West Lafayette, IN 47906

    765.463.1633 ext. 4444

    http://medinstitute.com/

     

     

     

     

     




    Original Message


  • 6.  RE: Biocompatibility

    Posted 17-Jul-2019 13:22
    Generally you do need to repeat testing. There are a couple reason for this, including:

    - it is very hard to say you processed the material in exactly the same way as the "proven" material. Think, for instance, an Ultem part that you mold. In this case "Ultem" may be proven, but your specific mold release (or cleaning process for the mold release) may not. Thus, regulators and standards tend to expect you can only leverage data if you can prove it was processed similarly. Another example may be materials that change leachables when heated - steam sterilization may result in different behavior than EtO or gamma.

    - the standards change and evolve over time and newer test methods may show sensitivities at lower levels than previously "established" materials. Note, for instance, the current questions around "metals" in implants. This is why you can't just use "Class VI testing" these days as evidence for your material.

    So in conclusion you should default to retesting and set the expectation that if you can "prove" equivalence you can leverage testing from a previously tested material.

    g-


    ------------------------------
    Ginger Glaser RAC
    Chief Technology Officer
    MN
    ------------------------------

    Original Message


  • 7.  RE: Biocompatibility

    Posted 18-Jul-2019 01:32
    Actually reading the standard would be helpful, particularly the 2019 version of ISO 10993-1 (though it is not the current consensus nor harmonized version, it does help expand on the use of information outside of testing, particularly in the case of animal testing).  Consideration should be given to the overall biological safety of the device, which is greater than some material selection, including device geometry, intended use and processing/manufacturing, in addition to the other factors already mentioned by others.

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    Christopher Erwin
    Scottsdale AZ
    United States
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    Original Message


  • 8.  RE: Biocompatibility

    Posted 19-Jul-2019 03:49
    Hi 

    The biological evaluation processed is performed in the finished product. This means that you do not evaluate only the raw materials, but also your entire process.
    Even if you have exactly the same materials with another manufacturer (which by itself is a very difficult task), you need to justify that you have exactly the same process (including production, sterilization, packaging etc) in order to waive testing. This will be very challenging, especially for implantable devices.
    On the other hand, if by performing chemical characterization, you can see whats going on with your device, retrieve all the toxicological information and make a solid justification to avoid some expensive and time-consuming tests.

    Hope that helps

    ------------------------------
    Spyros Drivelos
    Medical Devices Manager
    Agia Paraskevi, Athens
    Greece
    ------------------------------

    Original Message


  • 9.  RE: Biocompatibility

    This message was posted by a user wishing to remain anonymous
    Posted 17-Jun-2020 08:37
    This message was posted by a user wishing to remain anonymous

    Hi all, 
    Regarding testing labs, is there any requirement by the FDA that the lab should be ISO 17025 certified? 
    Thanks!
    Original Message


  • 10.  RE: Biocompatibility

    This message was posted by a user wishing to remain anonymous
    Posted 18-Jun-2020 08:09
    This message was posted by a user wishing to remain anonymous

    Hello,

    usually the FDA expects labs doing biocompatibility testing are working according to GLP (Good Laboratory Practice).

    Best Regards
    Original Message


  • 11.  RE: Biocompatibility

    This message was posted by a user wishing to remain anonymous
    Posted 18-Jun-2020 13:49
    This message was posted by a user wishing to remain anonymous

    Thanks. Can a lab do testing according to GLP but not be ISO 17025 accredited? Are these two things mutual inclusive?
    Original Message


  • 12.  RE: Biocompatibility

    Posted 19-Jun-2020 01:45
    In ISO 10993-1 it is mentioned that you should perform biocompatibility testing according to recognized quality practices, such as GLP or ISO 17025.
    It is not a mandatory requirement, but it is of course easier to prove the NB or FDA that your sub-contractor performs the tests under appropriate conditions and he is controlled by other independent agencies.

    There are a lot of laboratories with either GLP or ISO 17025 and there are also many who have both. It depends on the expertise and the orientation of the lab and the time and resources you want to spend.

    Hope that helps

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

    Original Message


  • 13.  RE: Biocompatibility

    This message was posted by a user wishing to remain anonymous
    Posted 19-Jun-2020 09:09
    This message was posted by a user wishing to remain anonymous

    Thanks, very helpful!
    Original Message


  • 14.  RE: Biocompatibility

    Posted 19-Jun-2020 10:06

    21 CFR Part 58(a) This part prescribes good laboratory practices for conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products. 

    I'm not aware of any FDA regulation that requires a lab be ISO 17025 certified.  That seems somewhat redundant, but there might be situations in which it would be useful, depending on the product.  I think the ISO certification grew up with labs that did chemical analysis/materials testing, probably for a range of industries, rather than for medical products per se, and problems arose when they tried to pursue the latter as if they were former.  In contrast, the GLP regulation was written specifically for FDA-regulated products.

    Interesting little overview here:
    ag.com/wp-content/uploads/2018/02/M-032518-GMP-GLP-or-ISO-17025-How-Do-These-Apply-to-Outsourced-Analytical-Testing.pdf



    ------------------------------
    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Mebane, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------

    Original Message


  • 15.  RE: Biocompatibility

    Posted 20-Jun-2020 07:48
    I was  the Regulatory/QA Director for a pre-clinical lab from 2006-2008 (Surpass) . At that time, SQA and FDA was looking at th feasibility of making testing labs install full quality  systems, and there was discussion whether ISO 9001 or ISO 17025 was more appropriate, since  GLPs under 21 CFR 58,  and 21 CFR 11 were in as requirements  anyway.   For studies that were to be submitted outside  the US, we also followed OECD requirements, and of course for all studies (both GLP and non-GLP) we followed requirements  of the US Animal Welfare Act AND the regulations under it.

    Labs fought  the suggestion they had to be certified to ISO 17025 or ISO 9001 back THEN, for the most part. If anything was to be applied,  we thought we "might" be able to live with ISO 17025.  But nothing other US GLPs, Part 11, and Animal Welfare Act is yet required at the moment.

    If you are just running early pre-clinical feasibility /screening studies to determine study design, etc..they do not have to be done  under GLPs unless  they are to be submitted in an application/submission. 

    But in my opinion, the closer your device gets to final prototype, you should be running under GLPs......if you have a Class 1 or other  Class device exempt from filing, you really need to do your biocomp/safety related studies  under GLP anyway.  Just my insider recommendation. 






    ------------------------------
    Ginger Cantor, MBA, RAC
    Founder/Principal Consultant
    Centaur Consulting LLC
    River Falls, Wisconsin 54022 USA
    715-307-1850
    centaurconsultingllc@gmail.com
    ------------------------------

    Original Message


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