CHemical RISk calculators (CHRIS) - Bulk chemicals (v2)

Identifier type and identifier - Please select the identifier type and enter the chemical identifier. For example, if the CAS number is known, select CAS from the pull down menu and enter the CAS number in the identifier field. If the CAS number is unknown, CHRIS can identify the molecular structure through the SMILES code, which can be found for many chemicals using PubChem or generated based on the molecular structure using tools such as OSRA. Alternatively, CHRIS can attempt to identify the chemical using a common name for the chemical.

Amount - Enter the total mass of the substance in the component being evaluated expressed in milligrams.

Matrix - Please select your polymer matrix from the list. If your polymer is not listed below, please select "Other 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.

Mass - Enter the mass of the polymer matrix in grams.

Density - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g. +/- 10%) is acceptable.

Exposed surface area - Enter the patient contacting surface area of the component being evaluated in square centimeters. This includes both direct and indirect patient contact.

Exposure type - Select the appropriate exposure category: > 30 days = long-term, > 24 hours - 30 days = prolonged, ≤ 24 hours = limited. For limited exposures (≤ 24 hours), please enter the maximum exposure time in hours.

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 - Because CHRIS 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 (e.g. residual monomers and oligomers, catalysts, initiators) or compounding (e.g. stabilizers, antioxidants, plasticizers) are within scope. Surface residuals from processing, cleaning, and sterilization are excluded. Further, any particles or aggregates must be small relative to the component and homogeneously distributed. This can be confirmed/justified 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 the chemicals are present only in dilute quantities. Confirming that the total amount of additives and impurities 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.