Catalog of Regulatory Science Tools to Help Assess New Medical Devices
The bulk chemical risk calculator enables users to conduct screening level risk assessments to aid in the biocompatibility evaluation of bulk additives and impurities in polymeric medical device components, excluding color additives.
These assessments can assist device manufacturers by providing immediate feedback on whether the presence of the bulk chemical would require additional justification and/or testing to demonstrate acceptable biological risk.
The output of bulk chemical risk calculator is a conservative margin of safety (MOS = toxicological safety limit ÷ exposure dose) value for a bulk chemical contained within a polymeric medical device component. Based on the MOS value, the calculator determines if further assessment of one or more biocompatibility endpoints is necessary for the specific chemical.
The bulk chemical risk calculator provides clinically relevant, yet still conservative, exposure dose estimates using a physics-based transport model for polymeric systems where transport data are available to support the use of the model. The model applies worst-case boundary conditions for release of a substance from the polymer matrix and is based on four primary assumptions:
- The clinical use environment does not cause the polymer matrix to swell or degrade,
- The chemical is homogeneously distributed throughout the polymer.
- The total amount of the chemical is present in dilute concentrations (<= 2 m/v %).
- Any particles/aggregates of the chemical present in the polymer are much smaller than the smallest component dimension (<= 50x).
While these assumptions are typically valid for bulk additives and impurities in biostable polymers, you must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system. Further, the bulk chemical risk calculator only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading). To estimate chemical release based on the model, the diffusion coefficient of the chemical in the polymer matrix must be specified. For the nineteen (19) polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of molecular weight, has been established based on data from the literature. For polymer matrices that are not included in this list, the bulk chemical risk calculator assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water.
Additional information is available on the Context of Use.
- Saylor, D. M., Chandrasekar, V., Simon, D. D., Turner, P., Markley, L. C., & Hood, A. M. (2019). Strategies for rapid risk assessment of color additives used in medical devices. Toxicological Sciences, 172(1), 201-212. https://doi.org/10.1093/toxsci/kfz179
- Saylor, D. M., Chandrasekar, V., Elder, R. M., & Hood, A. M. (2020). Advances in predicting patient exposure to medical device leachables. Medical Devices & Sensors, 3(1), e10063. https://doi.org/10.1002/mds3.10063
Because the bulk chemical risk calculator only addresses compounds with a distribution that is macroscopically homogeneous within the matrix, the tool can only be used to assess bulk additives and impurities. Therefore, only compounds that are introduced either intentionally or unintentionally during synthesis (such as residual monomers and oligomers, catalysts, initiators) or compounding (such as stabilizers, antioxidants, plasticizers) are within scope. Surface residuals from processing, cleaning, and sterilization are excluded. Also, the bulk chemical risk calculator requires the total amount of the chemical to be established in advance, e.g., based on a certificate of analysis. Furthermore, the bulk chemical risk calculator only addresses individual chemicals; therefore, a favorable outcome by the bulk chemical risk calculator does not imply acceptable biological risk for the final finished form of a medical device.
In addition to citing relevant publications, please reference the use of this tool using https://doi.org/10.5281/zenodo.6625802.