Real-Time Adaptive Inline Acidification Enhances Continuous pH Control for Viral Inactivation.

Existing low pH viral inactivation methods for continuous downstream processing of biologics typically rely on predictive models to estimate the necessary pH adjustments. However, these methods are of limited use during the process development stage due to the dynamic nature of capture chromatography, where batch variations can alter the eluted protein titer. This study introduces an inline viral inactivation system (IVIS) that utilizes real-time adaptive control and inline sensor readings to precisely regulate the pH manipulation for inline acidification and continuous viral inactivation.

Thermal and pH stress dictate distinct mechanisms of monoclonal antibody aggregation.

Protein aggregation is a significant challenge in the development of monoclonal antibodies (mAbs), which can be exacerbated by stress conditions encountered along its production pipeline. In this study, we examine how thermal and pH stress conditions influence mAb aggregation mechanisms. We observe a complex interplay between these factors that significantly affects mAb stability, particularly under combined stress conditions.

Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures.

Continuous manufacturing enables high volumetric productivities of biologics such as monoclonal antibodies. However, it is challenging to maintain both high viable cell densities and productivities at the same time for long culture durations. One of the key controls in a perfusion process is the perfusion rate which determines the nutrient availability and potentially controls the cell metabolism.

Leveraging an advanced simulated moving bed approach to achieve 3-component separation for enhanced impurity removal in a non-affinity cation exchange capture step.

One of the key challenges in downstream bioprocessing is to obtain products of high purity in a productive fashion through the effective removal of process and product related impurities. While a classical simulated moving bed (SMB) system operation can typically achieve a 2-component separation between the weakly bound impurities and target species, here we present an advanced SMB approach that can achieve a 3-component separation, including the removal of the strongly bound impurities from the target species. As a proof-of-concept, we demonstrate the enhanced removal of strongly bound host cell proteins (HCP) from the target monoclonal antibody (mAb) through the utilisation of the advanced SMB approach in a non-affinity cation exchange (CEX) capture step.