Enhancing Convergence and Diversity in Multi-Objective Particle Swarm Optimization with Cluster-Based Approach: Application to Hydrogen Production Process Optimization | AIChE

Enhancing Convergence and Diversity in Multi-Objective Particle Swarm Optimization with Cluster-Based Approach: Application to Hydrogen Production Process Optimization

Authors 

Hong, S. - Presenter, Yonsei University
Lee, J., Yonsei University
Recent improvements in cell lines, media, and bioreactor performance have led to large increases in product titer, creating significant challenges for the downstream purification process. This includes the virus filtration step, which is a critical component of the overall virus clearance strategy in the production of monoclonal antibodies (mAbs) and plasma-derived products. There is also growing interest in the possibility of performing virus filtration as part of the final fill-finish operations (in combination with the sterile filtration), which would provide added insurance against virus contamination while eliminating a separate stand-alone virus filtration step.

However, the capacity and fouling behavior of virus filtration at such high product titers (30 g/L or above) can be compromised by the formation of reversible and possibly irreversible product aggregates as well as by increased product-membrane interactions. In addition, increased viscosity or concentration polarization at high product titers could also reduce the flux.

Currently, the exact fouling mechanism that leads to significant flux decay is not understood. Here mAb feed streams at high product titers were characterized and correlated with virus filtration performance. The methods used include size exclusion chromatography, SDS PAGE and UV spectroscopic measurements. In addition, mAb solubility at different buffer conditions was determined. It was found that reversible product aggregates formed at high product titers are responsible largely for the flux decay during virus filtration.