When evaluating the biocompatibility of medical devices, the obvious set of standards and guidelines to refer to are those of the ISO 10993 series. However, in the past it has been challenging to place certain medical devices such as ventilators, breathing tubes and gas-mixing stations within the ISO 10993-1 framework. Nevertheless, for lack of a better option, these devices have been categorised as “external communicating devices” intended for contact with tissue and thus evaluated for a wide range of biocompatibility endpoints according to the ISO 10993-1 matrix. As many of these endpoints are debatably not critical for such breathing devices, this approach has risked the generation of unnecessary animal testing. Furthermore, more critical potential hazards might have been missed in the biological risk evaluation process that are not specifically highlighted in the key ISO 10993 matrix.

One key area of toxicological risk assessment for such breathing devices is the evaluation of volatile emissions, particles, condensates and leachables from the components of the device that may enter the gas pathway and subsequently become inhaled by patients. To address these gaps in the biological evaluation process, ISO has published ISO 18562; a relatively new four-part series of guidelines for the biocompatibility evaluation of breathing gas pathways in healthcare applications. Each section of the ISO 18562 series addresses a potential hazard that is specifically associated with the breathing gas pathway. These new guidelines should be consulted for every component or material of a medical device that contacts any gas stream that is delivered to patients (e.g. tubing, filters, connectors and facemasks). They describe certain chemical analyses that should be performed to identify any particulate matter, volatile organic chemicals (VOCs) and leachables that might potentially be inhaled by patients, and therefore possibly pose a toxicological hazard.

Once the analytical laboratories have identified such chemical substances in accordance with ISO 18562, it is important to then conduct a toxicological risk assessment (TRA) in line with Part 17 of the ISO 10993 series. See our description of this TRA process in our previous blog.

For substances detected by the analytical labs that are not identified confidently, ISO 18562-1 proposes Threshold of Toxicological Concern (TTC) values specifically for the inhalation route of exposure. These include values of 360, 120 and 1.5 µg/day for limited (<24 hour), prolonged (24 hours – 30 days) and permanent/long-term (>30 days) exposures. ISO 18652 also proposes a “practical” long-term threshold of 40 µg/day for chemically-identified (but not toxicologically tested) volatile organic species (VOCs). Presumably these should not contain any alerts for mutagenicity.

The evaluation of such chemicals is a core competence at bibra.

If you are interested to hear more about how to assess the biocompatibility of your medical devices, or require a toxicological risk evaluation, please get in touch.



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