(55a) Recent Advances and Current Directions in Downstream Processing for Biotherapeutics

Separation is increasingly becoming a bottleneck during the process development and production of biotherapeutics. Alternative separation technologies such as columnless chromatography, crystallization, precipitation, and countercurrent multi-stage aqueous two-phase extraction are being developed with the potential to significantly reduce process development time and/or costs. The particular characteristics of biotherapeutics pose increased challenges for the development of bioseparation technologies. Mechanistic modeling and experimental results are presented that demonstrate the promise of novel downstream technologies, which are supported by model-based optimal design and control. The technologies are demonstrated for multiple biotherapeutics including monoclonal antibodies, vaccines, and gene therapies.