Predictive mechanistic modeling of loading and elution in protein A chromatography.

Protein A chromatography is an enabling technology in current manufacturing processes of monoclonal antibodies (mAbs) and mAb derivatives, largely due to its ability to reduce the levels of process-related impurities by several orders of magnitude. Despite its widespread application, the use of mathematical modeling capable of accurately predicting the full protein A chromatographic process, including loading, post-loading wash and elution stages, has been limited. This work describes a mechanistic modeling approach utilizing the general rate model (GRM), the capabilities of which are explored and optimized using two isotherm models.

Engineering protein A ligands to mitigate antibody loss during high-pH washes in protein A chromatography.

Protein A chromatography is a workhorse in monoclonal antibody (mAb) manufacture since it provides effective separation of mAbs from impurities such as host-cell proteins (HCPs) in a single capture step. HCP clearance can be aided by the inclusion of a wash step prior to low-pH elution. Although high-pH washes can be effective in removing additional HCPs from the loaded column, they may also contribute to a reduced mAb yield.