Disclaimer: CHRIS is only addresses risk associated with the presence of color additives. Therefore, a favorable outcome by CHRIS does not imply acceptable biological risk for a finished, sterilized device. Further, a successful CHRIS evaluation does not address local biocompatibility endpoints, and therefore additional testing may be needed despite a positive outcome from CHRIS.
Identity - Select the color additive in the component being evaluated via the pull down list. If the color additive is not explicitly listed, please choose either "unlisted metal oxide" or "unlisted other". If "unlisted other" is selected, please enter the molecular weight of the color additive in grams per mole.
Amount - Enter the total mass of color additive in the component being evaluated expressed in milligrams.
Concentration - Enter the concentration of color additive in the component being evaluated expressed in milligrams of color additive per cubic centimeter of the component.
Please enter the combined concentration of all impurities in the color additive as a percentage (% mass/mass).
Total impurity concentration (%):
Please select your polymer matrix from the list below. If your polymer is
not listed below, please select "Unlisted polymer". For polymer mixtures/blends, co-polymers, or composites (e.g. glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e. the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.
Exposed surface area - Enter the patient contacting surface area of the color additive containing component being evaluated in square centimeters. This includes both direct and indirect patient contact.
Exposure type - Select the appropriate exposure category: > 30 days = permanent, > 24 hours - 30 days = prolonged, ≤ 24 hours = limited. For limited exposures (≤ 24 hours), please enter the maximum exposure time in hours.
Patient type - Please select the appropriate patient population for your device. This selection is used to determine the appropriate patient weight to be used to compute the pTE (mg/day) from a pTI value (mg/kg/day). The weights used by the calculator include: adults = 50 kg, pediatrics = 2.2 kg, and neonates = 0.5 kg, and the most conservative category (i.e. lowest weight) that may apply should be selected. For devices where none of these categories are appropriate for the intended patient population (e.g. obese patients), the user may select “other” and enter a specific weight in kg.
Exposed surface area (cm2):
⇒ Exposure time (h):
⇒ Patient weight (kg):
The exposure model relies on assumptions that are typically valid for color additive containing 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 compatibilility 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; 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 cofficient, which assumes any color additives are present only in dilute quantities. Confirming that the total amount of color additive 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 color additive concentration in excess of 2 m/v %, if the presence of additional color additives 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.
Check all statements below that are applicable to your color additive containing component:
The clinical use environment does not cause the polymer matrix to swell or degrade.
Color additive particles/aggregates are much smaller than the smallest component dimension (≤ 50x).
The color additive is homogeneously distributed throughout the polymer.
The total amount of color additive is present in dilute concentrations (≤ 2 m/v %).
Manufacturing processes do not impact the stability of the polymer.