Accelerated process development for integrated end to end biologics manufacturing

With the exception of monoclonal antibodies, biologics typically require bespoke manufacturing processes that vary widely in the type of and number of unit operations. This constraint leads to custom facility designs and unique strategies for process development for every new molecule. To enable flexible, multi-product manufacturing facilities and to reduce the speed to clinic for new molecules, streamlined manufacturing processes and associated strategies for process development are needed. We have developed a bench-scale, integrated and automated manufacturing platform capable of rapidly producing a variety of recombinant proteins with phase-appropriate quality for early development 1. The system comprises three modules for fermentation via perfusion, straight-through chromatographic purification, and formulation. To facilitate the production of multiple products on the same system, we have also developed a holistic strategy for process design to manufacture new products in as few as twelve weeks after obtaining the product sequence. While upstream process development in our host (Pichia pastoris) has been relatively straightforward, there are not many tools currently available for developing fully integrated straight-through chromatographic processes. Therefore, we developed an in silico tool for the prediction of fully integrated purification processes based on a one-time collection of host-related data combined with conventional high-throughput chromatographic screening data for each new target molecule 2. We used this tool to develop fully integrated, end-to-end production processes for three molecules (hGH, IFNα-2b, and G …