Development of Mammalian Cell Perfusion Cultures at Lab Scale: From Orbitally Shaken Tubes to Benchtop Bioreactors

This chapter introduces the necessary concepts to develop mammalian cell perfusion cultures for the expression of therapeutic proteins at lab scale. We highlight the operation of the orbitally shaken tubes and of a classical glass vessel reactor system coupled to an external alternating tangential flow (ATF) device. Two different experiments can be performed in the shake-tube system: (1) the VCDmax experiment exploring the maximum achievable viable cell density at a given medium exchange rate and (2) the VCDSS experiment for the prediction of process performance at constant viable cell density and a given medium exchange rate for the design of the benchtop bioreactor process. In addition, the operation of the benchtop system is discussed containing start-up and control procedures for a long-term production run.