Affinity chromatography such as Protein A affinity chromatography is an important step in the purification of monoclonal antibodies (mAbs) and mAb-derived biopharmaceuticals. While the biopharma industry has extensive expertise in the operation of Protein A chromatography, the mechanistic understanding of the adsorption/desorption processes is still limited and scaling up and scaling down can be challenging. Benner et al. (2019) describes mass transfer effects in bead-based resins as one possible explanation for the latter. With the advent of convective media such as Fibro technology, complex mass transfer and pore diffusion technologies are about to go obsolete. Fibro technologies drastically simplify the application of mechanistic modeling, since only the macroscopic fluid dynamics of the Fibro unit and the thermodynamic binding effects are left to be elucidated.<br/>In a collaborative study, we performed extensive experimental campaigns with varying cycles and mAb feedstock. The results form the basis for mechanistic modeling of the mAb adsorption and elution behavior, leadingto a predictive pH-extended stoichiometric model. Although only few runs were performed to develop the model, the simulation results provide accurate predictions for varying scales with high accuracy<br/>In summary, the results show how fiber-based Protein A systems and processes can be developed quickly with limited material expenditure and how reliable scale-up and scale-down can be predicted with high accuracy using a mechanistic model.

Affinity chromatography predictive scaling using miniature Fibro units and mechanistic modeling

ACS Fall 2021

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