文摘
Although fed-batch suspension culture of animal cells continues to be of industrialimportance for the large scale production of pharmaceutical products, existing controlconcepts are still insufficient. Changes in cell metabolism during cultivation andbetween similar cultivations, the complexity of the cell metabolism, and the lack ofon-line state variables restrict the transfer of available control strategies establishedin bioprocess engineering. A process control strategy designed to achieve optimizedprocess control must account for all these difficulties and fit sophisticated requirementstoward adaptability and flexibility. The combination of a fed-batch process and anOpen-Loop-Feedback-Optimal (OLFO) control provides a new approach for cell cultureprocess control that couples an efficient cultivation concept to a capable process controlstrategy. The application of an adaptive, model-based OLFO controller to a hybridomacultivation and experimental results are presented.