Ultrafiltration / Diafiltration of mAbs

Ultrafiltration and diafiltration are currently used for the final concentration and formulation of essentially all biotherapeutics.  However, recent trends in the production of monoclonal antibodies (mAbs) and antibody-derived products (e.g., Fc-fusion proteins) has led to the use of very highly concentrated formulations with protein concentrations in excess of 200 g/L. These highly concentrated formulations can have very high viscosities, creating challenges in processing (e.g., by ultrafiltration), storage (e.g., enhanced aggregation), and delivery (e.g., injection through small bore needles). This project is focused on identifying the key intermolecular interactions governing the behavior of these highly concentrated formulations, with a specific emphasis on the factors controlling the filtrate flux, maximum achievable protein concentration, and excipient partitioning during the ultrafiltration process.

 

Baek, Y., N. Singh, A. Arunkumar, A.L. Zydney, “Ultrafiltration behavior of an Fc-fusion protein: Filtrate flux data and modeling,” J. Membrane Sci., 528: 171-177 (2017).

Baek, Y., N. Singh, A. Arunkumar, A.L. Zydney, “Effects of histidine and sucrose on the biophysical properties of a monoclonal antibody,” Pharm. Res., 34: 629-639 (2017).

Baek, Y., N. Singh, A. Arunkumar, M. Borys, Z.J. Li, A.L. Zydney, “Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins: Effects of physical properties,” Biotech Bioeng., 114: 2057-2065 (2017).

Baek, Y., D. Yang, N. Singh, A. Arunkumar, S. Ghose, Z.J. Li, A.L. Zydney, “Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins: Effects of physical properties,” Biotech. Prog. in press (2017).