Membrane bioreactor separator system for integrated IgG fragmentation and Fab purification

This paper discusses a membrane based bioreactor system for producing pure Fab from human IgG. The bioreactor consisted of a stack of microporous anion-exchange membrane discs housed in a temperature controlled module. IgG was adsorbed on the membrane followed by its fragmentation with papain under optimized conditions. Fab was recovered in the reaction flow through while other fragments remained membrane bound and were subsequently eluted using high salt concentration buffer. By using the membrane bioreactor–separator system the overall process for producing Fab was simplified and high product purity and recovery were achieved. The pH of the feed solution had a significant effect on Fab recovery. The rate of IgG fragmentation by papain observed with the membrane bioreactor was about three times higher than that in an equivalent liquid phase reaction.