A simple design procedure is proposed that can be used to enhance the performance of a biological cultivation process. The model-supported method starts with a simple model. This is used to design first experiment, i.e., to calculate such a control profile that improves the process performance. The results of the experiment are then used to update the model and subsequently the control profiles. The procedure was first tested at simulated Saccharomyces cerevisiae and Penicillum chrysogenum cultivation processes and then practically applied to optimize an E. coli cultivation.