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  • 1.  extractables and leachables

    This message was posted by a user wishing to remain anonymous
    Posted 19-Feb-2019 09:28
    This message was posted by a user wishing to remain anonymous

    Hi all, 
    When is test on extractables and leachables needed?
    In the case of an external device that has surface skin contact (<24 h) only with the practitioner (not the patient), I know from the FDA guidance that cytotoxicity, Irritation and skin sensitization apply.

    I don't have clear thought if the following apply as well: 
    EN/ISO 10993- 13 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices
    EN/ISO 10993- 16 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables
    EN/ISO 10993- 17 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
    EN/ISO 10993- 18 Biological evaluation of medical devices – Part 18: Chemical characterization of materials
    Please advise,
    Thanks


  • 2.  RE: extractables and leachables

    Posted 19-Feb-2019 15:35
    Hi,

    The FDA guidance on the 'Use of ISO 10993-1' is really helpful, but in your case I would consider first reading ISO 10993-1, especially version 2018.

    The scope of the standard (section 1) tells you: This document applies to MDs that have direct or indirect contact with 
    - the patient's body during intended use;
    - the user's body, if the MD is intended for protection (...)

    If your risk assessment identifies possible biological adverse effects for the user, of course you could use ISO 10993-1 as well for risk mitigation.
    But it may be worth to double check if ISO 10993-1 really applies to your device. There is also an additional note in section 5.2.2 how to deal with devices that come into contact with the users ungloved hands.

    As far as I know E&L testing can not be used to address local effects like sensitization or irritation. I would love to learn something different from the RAPS crowd because I personally do not like in-vivo tests that much. 

    Based on the biological risks you identify in combination with the table in Appendix A you can define the endpoints you need to consider further on. From there you can dive into other standards from the 10993-series. 
    Read ISO 10993-1 carefully: It tells you in various sections when to consider specific biological endpoints, e.g. section 6.1 tells you when to consider degradation products.

    Kind regards,
    Michael

    ------------------------------
    Michael Hottner
    Köln
    Germany
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    Original Message


  • 3.  RE: extractables and leachables

    Posted 20-Feb-2019 04:45
    Hi Anon,

    During the biological evaluation of the device, you should take into account all the possible hazards, including the material(s) of manufacture; intended additives, process contaminants and residues (see ISO 10993-7 for ethylene oxide residues); leachable substances (see ISO 10993-17); degradation products (see ISO 10993-9, for general principles and 10993-13, 10993-14 and 10993-15 for degradation products from polymers, ceramics and metals, respectively); etc.

    ISO 10993-1 provide you guidance concerning the methodology of the biological evaluation you have to follow. Table A.1 of Annex A is only informative, which means that you have to address the given biological endpoints into your risk assessment and not necessarily perform those studies.
    If you perform Chemical Characterization (ISO 10993-18), which is basically a L&E study, you can potentially avoid additional testing such as genotoxicity or chronic toxicity studies, but unfortunately not the basics (cytotoxicity, irritation, sensitization). But for irritation and sensitization, combining the chemical characterization with in silico and in vitro studies, you can build a strong case and avoid in vivo studies. European Notified Bodies and competent authorities are more open to in vitro studies. I think FDA is more strict to that.

    Hope that helps

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


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