DESIGN OF RECOMBINANT PROTEIN PRODUCTION PROCESSES

A model-aided process design and supervision technique is proposed. Its efficiency is demonstrated by a nontrivial example, the development of a production process for the light chain of the antibody MAK33. This protein was expressed by the genetically modified E. coli B pUBS520 p12023 bacteria under the control of the tac promoter where lactose was used for induction. It is shown in this example that data from a few experiments are sufficient to develop a satisfactory production process. The development of process models, which are prerequisite for a systematic optimization of protein production processes, as well as their use for the determination of quasi-optimal feed-forward control profiles, is discussed. Model-supported closed-loop control is shown to lead to another improvement. Further performance enhancements can be obtained by changing the operational mode from the usually employed fed-batch procedure to a repeated fed-batch mode.