Bioprocesses are involved in producing different pharmaceutical products. Complicated dynamics, nonlinearity and non-stationarity make controlling them a very delicate task. The main control goal is to get a pure product with a high concentration, which commonly is achieved by regulating temperature or pH at certain levels. This paper discusses model predictive control (MPC) based on a detailed unstructured model for penicillin production in a fed-batch fermentor. The novel approach used here is to use the inverse of penicillin concentration as a cost function instead of a common quadratic regulating one in an optimization block. The result of applying the obtained controller has been displayed and compared with the results of an auto-tuned PID controller used in previous works. Moreover, to avoid high computational cost, the nonlinear model is substituted with neuro-fuzzy piecewise linear models obtained from a method called locally linear model tree (LoLiMoT). (C) 2009 Elsevier Ltd. All rights reserved.