Bioseparation in antibody manufacturing: the good, the bad and the ugly.

Improvements in upstream production have boosted productivity in the biomanufacturing industry, but this is leading to bottlenecks in downstream processing as current technology platforms reach their limits of throughput and scalability. Although chromatography remains an indispensible component of downstream processing due to its simplicity and high resolving power (The Good), there is virtually no economy of scale effect so more product translates almost linearly into greater production costs. Bind-and-elute processes (such as the initial capture step in antibody manufacturing) are volume-driven and therefore have knock-on effects that impact on the entire production facility since the space required for preparation, storage, and cleaning steps has to be similarly adapted (The Bad). During long-term operations with multiple cycles, thorough cleaning is necessary to prevent progressive fouling and microbial contamination (The Ugly). Innovative solutions are required, which may include revisiting simpler and less expensive separation technologies, the use of disposable modules, and the integration of improved processes that are scalable to cope with increased demands. Among the alternatives that have been put forward, membrane adsorbers are beginning to make a real impact on the industry, particularly for flow-through applications such as polishing and viral clearance.