Dose accuracy, parenteral material administration compatibility, surfactant choices, and formulation development in...

Making positive-impact formulation decisions for antibodies and integrated design of clinical durability creates a better drug product (DP). The goal of this study was to prevent dose loss to surfaces during clinical administration, especially when surfactant and/or antibody levels were low or when stressors were present. Studied here were 6 common polymers coated on QCM sensors in the presence of varying DP solutions to study surface interactions. Three immuno-oncology antibody DPs in-use sterile conditions were characterized: one intravenously (IV) at low polysorbate 20 (PS, PS20) concentration and varying antibody concentration, one IV at low, constant antibody concentration and varying concentrations of PS20, and another with constant PS20 to antibody ratio diluted subcutaneously (SC). Experiments mimicked clinical conditions, and characterized the impact of inline filtration, dilution, stressor forces, interaction behavior at interfaces, and adsorption during both administration types. Formulations and dilutions with and without antibody or PS20 were studied to estimate individual substance mass contribution at the surface. By laddering protein and/or PS20 concentrations, a method to find the minimum antibody or surfactant concentration was found. An adsorption model for DPs in clinic was formed to characterize protein loss and adsorption.