(548d) Impurity Removal in a Mab Process Using Depth Filtration Following Protein A

The use of depth filters for cell culture supernatant clarification in the biopharmaceutical industry is an established and well characterized process.  Recently, the usefulness of a depth filter to remove impurities when placed downstream of the capture step has been demonstrated after a change of polishing steps in one of our monoclonal antibodies led to increased levels CHO HCP, in the final product.  Experiments were performed to characterize HCP levels after the addition of an EMD Millipore X0HC depth filter to this purification process post capture.  The effectiveness of the X0HC depth filter to reduce HCP to comparable or better levels than those seen in the previous process was demonstrated and characterized at bench scale.  This process was then successfully transferred to both the 130-L and 1,000-L scales.  These initial data led to additional studies that examined whether the anion exchange flowthrough chromatography step used in this updated process was redundant.  Subsequent tests showed no detectable differences for HCP, DNA, or residual protein A in the final product produced from updated purification streams with and without the anion exchange chromatography step at bench scale.  These experiments suggested that the anion exchange chromatography step is a redundant step if a depth filter is used post capture step in a monoclonal antibody purification process.  Additional testing, including the validation of viral clearance, further characterization of depth filtration process parameters, and scale up are necessary to validate the feasibility of this type of implementation.