Improved HCP Reduction Using a New, All-Synthetic Depth Filtration Media Within an Antibody Purification Process.

Abstract

Biologic manufacturing processes typically employ clarification technologies like depth filtration to remove insoluble and soluble impurities. Conventional depth filtration media used in these processes contain naturally-derived components like diatomaceous earth and cellulose. These components may introduce performance variability and contribute extractable/leachable components like beta-glucans that could interfere with limulus amebocyte lysate endotoxin assays. Recently a novel, all-synthetic depth filtration media is developed (Millistak+® HC Pro X0SP) that may improve process consistency, efficiency, and drug substance product quality by reducing soluble process impurities. This new media is evaluated against commercially available benchmark filters containing naturally-derived components (Millistak+® HC X0HC and B1HC). Using model proteins, the synthetic media demonstrates increased binding capacity of positively charged proteins (72-126 mg g-1 media) compared to conventional media (0.3-8.6 mg g-1 media); and similar values for negatively charged species (1.3-5.6 mg g-1 media). Several CHO-derived monoclonal antibodies (mAbs) or mAb-like molecules are also evaluated. The X0SP filtration performance behaves similarly to benchmarks, and exhibits improved HCP reduction (at least 50% in 55% of cases tested). X0SP filtrates contained increased silicon extractables relative to benchmarks, but these were readily removed downstream. Finally, the X0SP devices demonstrates suitable lot-to-lot robustness when specific media components are altered intentionally to manufacturing specification limits.