Depth filtration is commonly employed in biologics manufacturing processes to remove insoluble and soluble impurities. The harvest depth filters with different pore sizes are usually used to retain cells and cell debris with wide range of sizes. In addition, depth filters with certain adsorptive characteristics may help retain process-related impurities such as host cell proteins (HCP) and DNA, as well as undesired product-related impurities such as high or low molecular weight (HMW, LMW) species. The strength and mechanism of the binding of species to the filter are affected by the properties of molecules involved as well as the characteristics of filters used. In our study, significant amount of LMW, mainly light chain species, was found in a bispecific cell culture fluid, posing burden to the subsequent downstream polishing steps. Therefore, it was desired to remove the majority of LMW at the harvest depth filtration step. A set of depth filters was found to be able to retain significant amount of LMW species with low amount of main product retained. The retention capacity of product and LMW species on the depth filters was studied followed by investigating their retention mechanism. Furthermore, different level of retention observed for these species was correlated to their different molecular properties in relation with adsorptive characteristics of the depth filters used.

Low molecular weight species removal via harvest depth filtration for a bispecific molecule

ACS Spring 2022

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