Impact of assay selection and study design on the outcome of cytotoxicity testing of medical devices: The case of multi-purpose vision care solutions

Medical device biocompatibility testing usually includes a cytotoxicity component. Assay selection and protocol design often depend on a specific testing standard rather than on the characteristics of the medical device. To better understand the impact of assay selection on study outcome of unstructured medical devices, we evaluated contact lens multi-purpose solutions (MPS) in the agar diffusion, direct contact and two elution cytotoxicity assays. To simulate the conditions of use, MPS were evaluated alone and in combination with contact lenses. All MPS passed the agar diffusion assay (n = 3) and extracts prepared from contact lenses soaked in MPS passed the USP elution assay (n = 3). Both the duration of contact and MPS concentration impacted the outcome of a modified elution assay. When tested at 25% strength for 48 h, all MPS evaluated were non-cytotoxic (n > 3). Test article movement and mechanical damage were significant issues with the direct contact assay. Movement was effectively controlled by manipulating contact lens orientation while using 0.8 mL culture medium. All MPS passed the USP direct contact cytotoxicity test when evaluated using this optimized methodology (n = 3). These data are consistent with MPS results in ocular irritation studies in rabbits (n = 3).