The University of ManchesterCarlos Alberto Duran VillalobosDoctor of Philosophy in the Faculty of Engineering and Physical SciencesDecember 2015This thesis presents an innovative batch-to-batch optimisation technique that was able to improve the productivity of two benchmark fed-batch fermentation simulators: Saccharomyces cerevisiae and Penicillin production. In developing the proposed technique, several important challenges needed to be addressed:For example, the technique relied on the use of a linear Multiway Partial Least Squares (MPLS) model to adapt from one operating region to another as productivity increased to estimate the end-point quality of each batch accurately. The proposed optimisation technique utilises a Quadratic Programming (QP) formulation to calculate the Manipulated Variable Trajectory (MVT) from one batch to the next. The main advantage of the proposed optimisation technique compared with other approaches that have been published was the increase of yield and the reduction of convergence speed to obtain an optimal MVT. Validity Constraints were also included into the batch-to-batch optimisation to restrict the QP calculations to the space only described by useful predictions of the MPLS model. The results from experiments over the two simulators showed that the validity constraints slowed the rate of convergence of the optimisation technique and in some cases resulted in a slight reduction in final yield. However, the introduction of the validity constraints did improve the consistency of the batch optimisation. Another important contribution of this thesis were a series of experiments that were implemented utilising a variety of smoothing techniques used in MPLS modelling combined with the proposed batch-to-batch optimisation technique. From the results of these experiments, it was clear that the MPLS model prediction accuracy did not significantly improve using these smoothing techniques. However, the batch-to-batch optimisation technique did show improvements when filtering was implemented.