Product-related impurity are challenging to remove during monoclonal antibody (mAb) purification process due to molecular similarity. Frontal chromatography on hydrophobic interaction resins has demonstrated its capability to effectively remove such impurities. However, process improvements geared towards purity comes as a trade-off with the yield loss. In this work, we present a hydrophobic interaction chromatography process using multicolumn continuous chromatography (MCC) concept and frontal analysis to remove a high prevalence product related impurity. This design uses a two-column continuous system where the two columns are directly connected during chase step to capture product wash loss without any in-process adjustment. One challenge associated with polish MCC design is that the accumulation of the impurities renders a non-steady state recycling. To surmount this issue and ensure a robust process, a mechanistic model was developed and validated to predict multicomponent breakthrough. This model was capable to predict multiple cycle behavior and accounts for increased impurity concentration. Assisted by the model, the optimized operation parameters and conditions can be determined to account for variation in product load quality. The results demonstrate that frontal analysis along with MCC polish step design can provide better trade-off between purity and yield while improving productivity compared to a classic batch mode.

Mechanistic insights into continuous frontal chromatography for mAb product variant separation

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.