ISO 10993-18:2020 pdf download – Biological evaluation of medicaldevices — Part 18: Chemical characterization of medical device materials within a risk management process.
5.9 Assess the actual chemical release (leachables profile)
Results of leachables studies, including both targeted leachables and leachables revealed by screening at levels above the AET, shall be reported so that the potential risks attributable to each constituent released can be assessed according to ISO 10993.17. ISO 10993.1 and ISO 14971.
5.10 Exiting the chemical characterization process
If the chemical characterization supports equivalence, or a toxicological risk assessment conclusion (per ISO 10993-17) that constituents, extractables, orleachables present an acceptable health risk, then the chemical characterization process has been completed and this outcome can be used to support biological evaluation under ISO 10993-1.
If the chemical characterization does not support a toxicological risk assessment conclusion (per ISO 10993-17) that constituents, extractables, or leachables present an acceptable health risk, the chemical characterization process has been completed but cannot be used to support biological evaluation. The need for further assessment (e.g. biological testing) or other mitigation activity should be evaluated per ISO 10993-1 and ISO 10993-17.
6 Chemical characterization parameters and methods
6.1 General 5 describes the stepwise generation of qualitative and quantitative chemical characterization data for use in the risk assessment. The characterization parameters to he used should be appropriate to the material or finished medical device. Due to the diversity of medical devices, It is recognized that not all of the parameters identified for a material will be required for all/some medical device uses. As noted previously, the extent of characterization required is determined by the invasiveness and duration of clinical exposure in the intended use (see ISO 10993-1:2018, 6.1). The type and amount of characterization data should be consistent with all of the parameters considered relevant to the risk assessment of the medical device and should consider the clinical application.
Chemical characterization data can be collected by information gathering from supplier information or literature review, or produced by information generation through testing a medical device or material directly in its natural state (e.g. IR analysis of a film). However, it is often necessary to solubilize all or part of the test article prior to analysis. The type and extent of solubilization employed shall match the intent and purpose of the testing. For example, if the purpose is to:
— generate information on the composition of a material (e.g. additives, residuals), then the appropriate sc)Iuhlllsatlon could Involve complete dissolution or exhaustive extraction of the test article;
— establish the presence of elemental impurities in the material, then digestion of the material could be appropriate;
— establish the test article’s extractables profile, then complete dissolution is inappropriate, and exhaustive, exaggerated, accelerated or simulated-use extraction. Is appropriate.
Additionally, the vehicles/media used for solubilisation should he considered in the context of the methods chosen [or testing those extracts, as the vehicles should be compatible with the test methods employed to analyse the extracts. If visible particles or precipitates occur during extraction, and are not soluhilized, these should be analysed as well, using applicable methods.
Due to the diversity of medical devices, their materials of construction and the conditions or their clinical use, it is recognized that extraction conditions suitable for simulating, accelerating or exaggerating clinical use will vary greatly. Nevertheless, Annex D provides considerations in determining extraction parameters for typical medical devices, including the choice of extraction vehicle, based on type of contact and duration of exposure.
A potential shortcoming in the ICP analysis is that it does not reveal the form in which the elementexists. This could complicate the toxicological risk assessment of ICP data in certain (but not all)circumstances.For example, sulphur can be extracted as elemental sulphur, as the sulphate ion or as apart of an organic extractable (such as mercaptobenzothiazole). The chemical form of sulphur detectedin an ICP analysis can be necessary to perform the toxicological risk assessment, because the toxicologyof sulphur can depend on its form.