Automation of an integrated micro‐scale platform for monoclonal antibody process development by incorporation of a depth filter mimic

TL;DR

This paper presents an automated micro-scale platform for monoclonal antibody purification that integrates depth filtration, improving efficiency and reducing time and resources.

Contribution

The novel integration of a depth filtration mimic into an automated micro-scale platform for mAb process development.

Findings

The micro-scale platform achieved effective removal of host cell DNA and impurities comparable to lab-scale operations.

The platform reduced total run time by over 50% while maintaining product quality specifications.

It demonstrated robustness across varying impurity profiles, supporting diverse process intermediates.

Abstract

High throughput process development (HTPD) has been widely adopted for efficient development and optimization of chromatographic operations in monoclonal antibody (mAb) purification. However, the integration of non‐chromatographic unit operations, particularly depth filtration following protein A chromatography, which is essential for the removal of process‐ and product‐related impurities prior to the ion exchange chromatography (IEX) operations, remains a challenge due to the absence of commercially available micro‐scale depth filtration tools. This limits the integration of this unit operation within the purification sequence, restricting the analysis of process interactions and overall process understanding. In this study, a micro‐scale HTPD platform was designed and evaluated to enable integration of a depth filtration mimic, Sartobind® Q anion exchange adsorber, within a mAb purification sequence. This was achieved by translating laboratory‐scale protocols to the micro‐scale using workflow design tools and executed on an automated liquid handling system. Step yields and impurity clearance were assessed to confirm the equivalence of scale‐down. The Sartobind® Q membrane achieved effective removal of host cell DNA (hcDNA), while subsequent IEX operations removed host cell proteins (HCPs) and high molecular weight components (HMWC), meeting target product quality specifications. The platform demonstrated robustness across varying impurity profiles, supporting its applicability for diverse process intermediates. Comparative analysis with laboratory‐scale operations confirmed the performance and scalability of the micro‐scale system, reducing the total run time by greater than 50%. The integrated HTPD platform offers a resource‐efficient, scalable approach for comprehensive mAb purification process development and is suitable for developability assessments during early‐stage development.

Integrating non‐chromatographic operations, such as low pH viral inactivation and a depth filtration mimic, into an automated micro‐scale platform enhances productivity while reducing resource and time requirements. By facilitating rapid, data‐rich experimentation, the platform offers a powerful and efficient tool for assessing and optimizing monoclonal antibody (mAb) production processes.

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