Robust estimates of solute diffusivity in polymers for predicting patient exposure to medical device leachables

Author:

Elder Robert M.1ORCID,Saylor David M.1ORCID

Affiliation:

1. Center for Devices and Radiological Health, FDA Silver Spring Maryland USA

Abstract

AbstractMedical devices often include polymeric components, which contain additives or contaminants that may leach into patients and pose a health risk. Previously, we proposed a mass transport model that conservatively estimates the leaching kinetics and only requires the solute's diffusion coefficient in the polymer, , to be specified. Because determining experimentally is time‐consuming, we also parameterized empirical models to estimate worst‐case values using only the solute molecular weight, . These models were based on a modest database and were limited to 19 polymers and larger solutes ( g/mol). Here, we assemble a much larger database, which enables us to construct more accurate models using a robust statistical approach, expanding the coverage to 50 device‐relevant polymers and smaller solutes ( g/mol). Then, we demonstrate several applications of these bounds, including modeling the release kinetics. Finally, we observe an interesting phenomenon, a discontinuous drop in of up to 25,000× for solutes with g/mol in glassy polymers. Using molecular simulations and cheminformatics tools, we propose a novel definition of the effective diameter of free volume channels in polymers, and we show that solutes larger than this channel size diffuse much more slowly.

Publisher

Wiley

Subject

Materials Chemistry,Polymers and Plastics,Physical and Theoretical Chemistry

Reference309 articles.

1. US FDA FDA's Predictive Toxicology Roadmap.https://www.fda.gov/science-research/about-science-research-fda/fdas-predictive-toxicology-roadmap2019.

2. ISO 10993‐17.Biological evaluation of medical devices – Part 17: Establishment of allowable limits for leachable substances; Standard 2002 Vol. 2002.

3. ISO 10993‐18.Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process; Standard 2020 Vol. 2020.

4. ISO 10993‐12 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials; Standard 2012 Vol. 2012.

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