Biosorption of process-equipment-related leachables (PERLs) in biomanufacturing: A quantitative approach to study partitioning of PERLs in a cell culture system.

The assessment and potential risk of process equipment-related leachables (PERLs) in the production of biopharmaceuticals and cell therapeutics using single-use (SU) equipment has been discussed previously. However, potential interactions of cells with PERLs have not yet been considered. Here, we present a quantitative adsorption study of neutral, organic small-molecule leachable compounds - known for extractables & leachables (E&L) analysis of SU equipment - in aqueous suspensions of CHO and T cells. The solid-water partition coefficient K was obtained for all compounds that showed adsorption. The findings implied that hydrophobic interactions are dominant; however, there was no unambiguous correlation between the derived adsorption coefficient K and the octanol-water partition coefficient K. Interestingly, a maximum affinity of both cell types to the leachable bis(2,4-di-tert-butylphenyl)phosphate, which is known to be detrimental to cell development, was observed. A comparison of both cell types revealed that they generally interact with the same compounds in most cases but to different extents. Using partition coefficients enables estimation of the concentrations of leachable compounds associated with the biomass phase and in the aqueous suspensions and could be used for risk assessment of SU systems in biopharmaceutical and cell therapy (CT) manufacturing processes.