A systematic Quality by Design (QbD) strategy was used to develop and characterize a hydrophobic interaction chromatography (HIC) step in a monoclonal antibody production process to reduce levels of PLBL2, a well characterized CHO host cell protein that co-purified with the monoclonal antibody. The HIC step was implemented as the final chromatography unit operation in the purification process and was specifically introduced to reduce PLBL2 levels more than 100 fold while maintaining process manufacturability and product quality. A risk assessment based approach incorporating development data, manufacturing data, and manufacturing plant capability was used to define process parameters and ranges to include in multivariate characterization experiments. Characterization studies identified an operating space for the HIC unit operation, which consistently delivers levels of PLBL2 below or near the detection limit of the PLBL2 ELISA assay. A process linkage study was conducted to challenge ability of the HIC step to clear PLBL2 from worst-case pools coming from cell culture or other purification unit operations. A PLBL2 spike-removal study was used to further demonstrate effective clearance of this host cell protein. This presentation is a case study that demonstrates how the data generated support the multivariate acceptable parameter ranges for the HIC step to meet Drug Substance target ranges for this critical quality attribute (PLBL2).

Defining process design space for a therapeutic monoclonal antibody: Clearance of phospholipase B-Like 2 (PLBL2), a CHO host-cell protein impurity, by hydrophobic interaction chromatography

251st National Meeting (2016)

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