Fed-batch operation of fermentation processes has been receiving a great deal of interest as it offers the possibility to control a substrate concentration at a desired condition. However, control of a fed-batch fermentation reactor has been known to be a difficult task due to its highly nonlinear and complicated behavior. This work addresses an optimization-based control strategy for a fed-batch bioreactor where an ethanol fermentation process is chosen as a case study. The optimal control problem is formulated to determine the optimal feeding rate policy giving the highest product yield. The resulting optimization problem is solved by using an efficient sequential approach with a piecewise constant control parameterization. Due to the limitation of the sequential approach to cope with inequality path constraints, comparative studies of the methods for handling such constraints are carried out. Furthermore, the impact of time interval and switching time on the solution of the optimal control is investigated.