Design, Optimization, and Adaptive Control of Cell Culture Seed Trains.

For the production of biopharmaceuticals, a procedure called seed train or inoculum train is required to generate an adequate number of cells for the inoculation of the production bioreactor. This seed train is time- and cost-intensive but offers potential for optimization. A method and a protocol are described for seed train mapping, directed modeling, and simulation as well as its optimization regarding selected optimization criteria such as optimal points in time for cell passaging. Furthermore, the method can also be applied for the transfer of a seed train to a different production plant or the design of a new seed train, for example, for a new cell line. Another application is to support the selection of the optimal clone for a new process. Seed train prediction can be performed for different clones, and so it can be analyzed how the seed train protocol would look like and for which clones a suitable seed train protocol could be found.Although the chapter is directed toward suspension cell lines, the method is also generally applicable, e.g., for adherent cell lines.