CHRIS: CHemical RISk calculators - Extraction Efficiency

Context of Use (COU)

The extraction efficiency module of the CHemical RISk calculator (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 can 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 can support reducing the number of configurations that need to be tested for a device product line to support biocompatibility evaluation of a medical device. Further, the tool can potentially be used to guide the development of alternative extraction test protocols.

The CHRIS - extraction efficiency 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 a non-steady state mass transfer model. 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. For additional details on the model please see this article.

The tool is limited by the assumptions upon which the model is based. The salient limitations are enumerated below:

  1. 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). The model is not appropriate for surface residuals from processing, cleaning, and sterilization.
  2. The solvent is “perfectly mixed”. This should be a reasonable assumption provided the samples are adequately agitated over the timeframe of the testing. However, this assumption may not be appropriate if sufficient agitation is not applied and a signficant boundary layer develops that slows the release rate or if the extraction is conducted under flow conditions.
  3. 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.
  4. 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.