The production of biotherapeutics involves many unit operations, and it is common practice to store in-process material as dictated by the manufacturing setup and scheduling of unit operations.
The stability of in-process materials can vary widely, and it is important to maintain parameters such as bioactivity and stability throughout the entire process. When a target molecule is expressed as extracellular protein that is secreted into the bioreactor or fermentation broth, the unit operations of protein harvest and initial column capture can be combined to protect proteins with limited stability.
The elimination of storage requirements and susceptibility to any cooling or freeze/thaw cycles between these two unit operations can contribute to a more robust process. Already proven at bench-scale and now running at pilot-scale, scientists at GE Healthcare Life Sciences have used automated hardware and software to link two such processes together.
We found that both the initial clarification/diafiltration, using a microfilter, and the initial column capture step, using adsorptive chromatography, were completed in less than eight hours. If run traditionally as individual unit operations these steps would have required twice the time and storage of the target protein in between the two operations. In addition, we reduced the process time by 50% by using standard UNICORN™ software for both crossflow filtration on UniFlux™ to clarify and ÄKTApilot™ to purify a target protein from yeast in one day.