The exposure model relies on assumptions that are typically valid for bulk solutes in polymeric device components. However, if any of the assumptions are violated the exposure calculation may not remain protective. Therefore, if the output of CHRIS is used to support a submission to CDRH, users must confirm conformance to the underlying assumptions or provide supporting justification. Examples of considerations when confirming conformance are provided below:
Biostability of the matrix - While many of the matrices listed within CHRIS will not appreciably swell or degrade in any physiological environment, this can not be generalized. For example, silicones may swell in lipid-rich environments. Chemical compatibility of the polymer matrix with the use environment can be assessed based on historical use and/or evaluation of swelling and/or degradation propensity in physiologically relevant media.
Particle/aggregate size and distribution - CHRIS relies on the color additive having a distribution that is macroscopically homogeneous within the matrix (e.g. CAs used for surface marking would be excluded); thus, any particles or aggregates must be small relative to the component and homogeneously distributed. This can be confirmed/justified through the use of particle coatings and/or dispersants in the concentrate to prevent aggregation and promote homogeneity, macroscopic observations of color uniformity, and/or microscopic observations to evaluate the potential for surface segregation phenomena, such as blooming.
Dilute concentration - The model relies on a concentration independent diffusion coefficient, which assumes any color additives are present only in dilute quantities. Confirming that the total amount of color additives present is ≤ 2 m/v % is sufficient to conform with this assumption. It may be possible to justify that the CHRIS calculation for a dilute compound will remain protective if the total concentration is in excess of 2 m/v %, if the presence of additional compound could reasonably be expected to inhibit rather than promote diffusion, e.g. second phase particulates.
Matrix stability - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g. during sterilization) or other physicochemical changes (e.g. excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.