Catalog of Regulatory Science Tools to Help Assess New Medical Devices
This regulatory science tool presents a computer model that allows the user to compare the theoretical impact of extraction conditions, sample geometry and material properties on extraction efficiency and extraction solvent concentration.
Technical Description
The extraction efficiency module of the CHemical RISk calculator (CHRIS)External Link Disclaimer uses a non–steady state mass transport model to predict the extraction efficiency of bulk leachables from medical device polymers. The model requires eight (8) input fields that describe the extraction conditions, test article geometry, and test material system, including the mass, density and surface area of the test article, extraction solvent volume, extraction time, number of iterations, and the diffusion and partition coefficients that describe the system of interest. Using these input parameters, the module outputs a predicted extraction efficiency (mass of extractable released over the initial mass in the test article) and relative extract solvent concentration (concentration in the solvent over the initial concentration in the test article) based on the model. For additional details on the model please see this articleExternal Link Disclaimer.
Additional information is available in the Context of UseExternal Link Disclaimer.
Intended Purpose
The extraction efficiency module of the CHemical RISk calculators (CHRIS) allows the user to compare the theoretical impact of extraction conditions, sample geometry and material properties on extraction efficiency and extraction solvent concentration. These assessments may assist device manufacturers and test laboratories by providing immediate feedback on “worst-case” device geometries and extraction conditions based on the endpoint of interest. This information may also be useful for reducing the number of configurations that need to be tested for a medical device product line while assessing its biocompatibility profile. Further, the tool may potentially be used to guide the development of alternative extraction test protocols.
Testing
We have implemented a non–steady state mass transport model to predict the extraction efficiency of bulk leachables from medical device polymers. The model considers immersion in a well-mixed solvent for both single–step and iterative extraction methods. By exploring the range of model parameters for typical device extractions, we found that the fraction of leachable mass released can range from the parts per thousand range to complete exhaustion, and identified the parameter regimes where extraction testing will be dominated solely by either thermodynamic or kinetic contributions. We also predicted the impact of changing the size of the test article and extraction ratio. The results illustrated that changing extraction conditions can have a dramatic and sometimes opposing effect on total mass release and extraction solvent concentration, depending on material properties, emphasizing the need to consider how the extraction test results will be leveraged when establishing “worst–case” extraction conditions. For iterative/exhaustive extractions, the model predicts more iterations may be needed to reach exhaustion for shorter iteration times and samples with larger volume to surface area ratios, as well as extractions conducted with lower solvent to polymer volume ratios. Furthermore, the iterative extraction predictions suggested that two dimensionless parameters provide a good approximation to expected scaling relationships between the model parameters and fraction of mass release. These scaling relationships can be useful in developing and comparing different extraction protocols and sample geometries.
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Limitations
The tool is limited by the assumptions upon which the model is based. The salient limitations are enumerated below:
- The extractable is macroscopically homogeneous within the matrix. Therefore, the output is only applicable to compounds that are introduced either intentionally or unintentionally during synthesis (e.g., residual monomers and oligomers, catalysts, initiators) or compounding (e.g., stabilizers, antioxidants, plasticizers) are within scope. The model is not appropriate for surface residuals from processing, cleaning, and sterilization.
- The solvent is “perfectly mixed.” This should be a reasonable assumption provided the samples are adequately agitated in a static bath over the timeframe of the testing. However, this assumption may not be appropriate if sufficient agitation is not applied and a boundary layer develops that slows the release rate or if the extraction is conducted under flow conditions.
- Possible chemical reactions are not considered. Therefore, if the polymer matrix undergoes substantive degradation during the extraction test, the predictions may not be relevant. Further, the model does not consider the potential for individual extractable compounds to degrade over the selected timeframe.
- The test article is comprised of a single polymer matrix. In practice, complex devices may be comprised of multiple components and/or polymer matrices. In these scenarios, careful consideration of the potential contributions of each material constituent of the test article to the extractables profile is critical when attempting to leverage the model predictions.