A US-based medical devices manufacturer.
The client commissioned bibra to review a biocompatibility report following feedback from US FDA.
To review and provide additional input on a biocompatibility report conducted according to ISO 18562 guidelines on a nitric oxide delivery system.
Approach and outcome
Medical devices that form part of a breathing gas pathway require evaluation under the ISO 18562 guidelines - Biocompatibility evaluation of breathing gas pathways in healthcare applications.
Expert opinion on the existing report was provided by bibra toxicologists in a number of areas including the selection and adjustment of screening assessment benchmarks to reflect the highly sensitive patient sub-population (pre-term infant or neonate), the detailed justification of read-across surrogate/analogues, and additional hazard and risk characterisations for compounds where the Margin-of Safety (MoS) is toxicologically acceptable (>1) but “close to 1”.
Recommendations were made to expand the existing screening hazard characterisation, making use of (Q)SAR software, the European Chemicals Agency C&L Inventory and the EU Endocrine Disruptor Lists. This allowed endpoints considered critical for medical devices under the ISO 10993-1 guidelines to be flagged, including genotoxicity, carcinogenicity, local irritation of the respiratory tract, respiratory sensitisation, acute systemic toxicity, subacute/subchronic/chronic toxicity and reproductive and developmental toxicity. A discussion of exposure-based refinement of screening prioritisations and selection of health-critical extractables was also provided, as was an overview of the methodology for further assessment of those chemical considered (via the screening assessment) to be a health-critical.
Overall, it was concluded that the biocompatibility report had been conducted in general accordance with the ISO 18562 series of guidelines, and that the points raised by the US FDA had been partly addressed. The bibra team noted that a more complete response could have involved: the adjustment of relevant adult health-based guidance values (HBGVs) to accommodate the much smaller and potentially more sensitive patient subpopulation; the use of more appropriate HBGVs or the TTC for certain compounds; the provision of more detail and justification on read-across surrogates/analogues; and the provision of a more comprehensive hazard and risk characterisation for those compounds where the MoS is deemed “close to 1”.