This study considers the problem of manipulating in an optimal way the perfusion and bleed flow rates of a continuous culture of hybridoma cells, so as to achieve a fast transient start-up and reject potential disturbances. The proposed solution makes use of an analysis of the properties of the steady state solutions of the nonlinear dynamic model of the cell culture, and in particular the relationship between the two main limiting substrates, glucose and glutamine. The solution is implemented using extended prediction self-adaptive control. Simulation results demonstrate the approach potentiality.