Novel small scale TFF cell retention device for perfusion cell culture systems

Abstract

Background Perfusion processes have traditionally been used for the generation of unstable proteins in cell culture systems. The use of perfusion for production of stable proteins has been limited by low product concentration, media costs, and system complexity. With the advent of new single-use technology and high producing cell lines, perfusion processes are gaining increased attention from industry. Also, the enhanced productivity of perfusion bioreactor compared to fedbatch enables use of smaller single-use systems, both for clinical scale production as well as potentially for manufacturing scale. These new perfusion processes cannot only be used as a production platform but also for process intensification of fed-batch processes. Perfusion can be used to dramatically increase the cell density of the N-1 bioreactor to accelerate the production process and achieve gains in efficiency. The critical components of a perfusion system are the bioreactor controller, cell culture vessel, and cell retention device. The cell retention device or system is often used to define the type of perfusion system with gravitybased and filtration devices being the most common. This study will show the application of a small-scale tangential flow microfiltration device(prototype small scale ProstakTM) in a perfusion test platform. This prototype device was derived from EMD Millipore ProstakTMmicrofiltration family of products typically used in the primary clarification of cell culture.