ISO 10993 risk assessment of ester extractables from a medical device


An analytical lab working on the behalf of a medical devices manufacturer.


Extraction studies on a device used to transfer injectable medium identified several esters that could, as a worst case, leach over time into the contained fluid, and subsequently be injected into patients. Under ISO 10993-1, the device is in contact with the blood path indirectly for a “limited” duration (≤24 hours).

Project goals

Bibra was asked to assess the risks posed by the extracted esters to patient health, as part of a toxicological risk assessment (TRA) performed following ISO 10993-17 guidance.


As rapid metabolism of the esters was expected upon their entry into the blood, bibra calculated worst-case exposures to the ester hydrolysis products, as well as to the esters themselves. Structurally-similar chemicals thought to operate by the same toxicological mode of action (MoA) were grouped and evaluated together.

Weight-of-evidence evaluations allowed conclusions to be drawn on the genotoxic potential of each chemical. When genotoxicity could be excluded, appropriate points of departure (PoDs) were identified from Expert Group reviews, the primary literature, or using threshold of toxicological concern (TTC) concepts. These PoDs were used to calculate tolerable intake (TI) and tolerable exposure (TE) figures for adults, children and neonates. Conclusions on tolerability were based on margins of safety (MoSs) between the TEs and worst-case exposures.

Project outcome

No concerns for genotoxicity were raised by any of the assessed chemicals, and appropriate TI and TE figures were derived. In most cases, toxicity risks were negligible for adults, children and neonates, even if the esters are genuine leachables at the worst-case exposure levels calculated. For one extractable, a definitive opinion on tolerability for children and neonates could not be reached. Of course, the extraction studies may have vastly overestimated the level to which patients might be exposed to this chemical, and the results of future tests determining the extent (if any) to which it is a genuine leachable should prove useful in determining whether this extractable represents an actual concern for patient health.

Bibra project team

Beth O’Connell
Pete Watts


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