Single pass diafiltration integrated into a fully continuous mAb purification process.

Abstract

The concept of continuous manufacturing has gained significant interest from the biopharmaceutical industry over the past several years. Benefits include increased manufacturing productivity, improved quality control, reduction in plant footprint, and more flexible management of facility capacity. There are several technologies currently available that enable continuous processing for chromatography and ultrafiltration. However, a single pass diafiltration design that meets the required small molecule clearance and has been integrated into a fully continuous monoclonal antibody purification process has not been previously published. Here, the theory and design of a 3-stage single pass diafiltration step is presented. Buffer exchange greater than 99.75% was experimentally demonstrated. Several critical design aspects were incorporated to minimize system complexity and reduce the buffer volume requirements. Lastly, single pass diafiltration was demonstrated in a pilot scale continuous process with uninterrupted flow from the bioreactor through the formulation step. This work illustrates the feasibility of incorporating a single pass diafiltration step into an end-to-end continuous protein purification process.