Application of a High-Throughput Screening Procedure with PEG-Induced Precipitation to Compare Relative Protein Solubility During Formulation Development with IgG1 Monoclonal Antibodies

摘要: ABSTRACT: Protein solubility is a critical attribute in monoclonal antibody (mAb) formulation development as insolubility issues can negatively impact drug stability, activity, bioavailability, and immunogenicity. A high-throughput adaptation of an experimental method previously established the literature to determine apparent protein described, where polyethylene glycol (PEG) used reduce quantitatively definable manner. Utilizing automated, system, immunoglobulin G (IgG)1mAb variety buffer conditions was exposed increasing concentrations PEG amount remaining solution determined. Comparisons midpt values (the weight% required decrease concentration by 50%) extrapolated (in absence PEG) were performed. The determination using sigmoidal curve fitting entire data set shown be most precise reproducible approach for use during screening experiments. methodology then applied different formulations optimize relative profiles (weight% vs. their corresponding values) terms pH ions both human chimeric IgG1mAbs. Other comparisons included evaluating IgG1mAb produced from cell lines (Chinese hamster ovary murine) well IgG1mAbs (produced same line) series buffers. Based on these comparisons, it concluded that rapid, determinations practical, tool compare mAb preparations rank order development.