Leveraging Extraction Testing to Predict Patient Exposure to Polymeric Medical Device Leachables Using Physics-based...

Area of Science:

• Biomaterials Science
• Toxicology
• Chemical Engineering

Background:

• Toxicological risk assessment for polymeric medical devices increasingly replaces animal testing.
• In vitro extraction tests in aggressive conditions are used to estimate patient exposure, but clinical relevance is often unclear.
• Physics-based mass transport models offer a framework to interpret these tests for better clinical relevance.

Purpose of the Study:

• To demonstrate the quantification of material properties (diffusion (D) and partition coefficients (K)) using standard extraction testing.
• To evaluate the utility of these properties in parameterizing physics-based exposure models for medical devices.
• To assess the potential for more accurate and conservative patient exposure dose estimates.

Main Methods:

• Utilized high-density polyethylene systems with four additives for testing.
• Quantified diffusion (D) and partition coefficients (K) through standard extraction tests in hexane and isopropyl alcohol.
• Applied physics-based mass transport models to interpret extraction data and estimate patient exposure.

Main Results:

• Material properties (D and K) were successfully quantified and consistent with theoretical predictions.
• Physics-based models, parameterized with experimental data, yielded clinically relevant, conservative exposure estimates over 100 times lower than aggressive extraction conditions.
• Challenges and benefits of using extraction data for model parameterization were discussed.

Conclusions:

• Physics-based modeling can enhance the clinical relevance of toxicological risk assessments for medical devices by interpreting in vitro extraction data.
• This approach offers a pathway to more accurate and conservative patient exposure estimations.
• Further efforts in data aggregation and advanced modeling are needed for routine application of this framework.