10‐Fold Improvement in Depth Filter Capacity During Integrated Dynamic Bioprocessing (IDB) Purification Through Depth Filter Cycling and Precipitate Control Strategy

ABSTRACT

During bsAb1 purification, precipitate was formed during neutralization of the affinity capture product. This precipitate was removed before loading onto the first polishing column in the Integrated Dynamic Bioprocessing (IDB) platform. The precipitate had a dynamic particle size distribution that caused complex scaling without proper characterization. Herein, the study established a protocol for characterizing downstream precipitate formation and operating a depth filter (Emphaze AEX) like a chromatography column to support continuous purification of bsAb1. The depth filter is “underloaded” with precipitated material, followed by a chase step and the application of sanitization buffers. The sanitization buffers solubilized precipitate bound to the depth filter and controlled bioburden, drastically increasing the filter capacity and helped ensure a closed system. At the bench, the depth filter was cycled 40 times for a total capacity of 10,500 L/m ² . This capacity is an order of magnitude greater than when the depth filter is loaded to max capacity without any cycling or sanitization. The resulting cycling capacity eases depth filter scale‐up and IDB implementation at the clinical and commercial scale.