A simple optimization strategy is described which enables monoclonal antibody (MCA) production in hollow-fiber bioreactors to be controlled and predicted. The MCA production rate is demonstrated to increase linearly with the uptake rates of glucose and glutamine and with the production rates of lactate and ammonia. The uptake and production rates of these metabolites can, in turn, be predicted from the pumping rates of basal medium to the bioreactor. We recommend a period of 2 weeks at the start of the cultivation when intensive assaying and monitoring should be carried out. After this period, the medium flow rate and MCA production rate may be predicted by linear extrapolation.