Compositional profiling for biodegradable medical devices: a framework for degradation-informed exposure and risk assessment.

Biodegradable polymers (BPs) present unique challenges for chemical characterization and toxicological risk assessment. Methodological requirements for devices with prolonged tissue contact often involve exhaustive extraction-an approach impractical for many BPs due to their degradability and incompatibility with common solvents. This paper proposes a hybrid approach to TRA for BPs, beginning with compositional profiling to estimate the total quantity of each polymer in a device and applying worst-case assumptions for complete hydrolysis into monomeric constituents. A biodegradable vessel closure system composed of a glycolide-caprolactone-trimethylene carbonate (GA-CL-TMC) copolymer, combined with a poly(glycolide-lactide) (PLGA) suture and polyethylene glycol (PEG) sealant, is applied as a case study. Estimated exposure doses (EEDmax) are calculated for acute, subacute, subchronic, and chronic durations using the assumed release model defined in ISO 10993-17:2023. Where initial margins of safety (MOS) are low, refined exposure estimates are then derived using in vitro-in vivo correlation (IVIVC) data. Degradation-based release kinetics provide exposure scenarios that more accurately reflect in vivo conditions, offering a conservative yet physiologically plausible basis for acute and subacute exposure estimates. This approach demonstrates that compositional profiling, supplemented with IVIVC data, offers a practical and conservative framework for assessing systemic toxicological risk posed by BPs. These methods only account for BP degradation products and should be augmented with additional methods to address manufacturing residues.