One of the most important events in fed-batch fermentations is the definition of the moment to start the feeding. This paper presents a methodology for a rational selection of the architecture of an artificial intelligence (AI) system, based on a neural network committee (NNC), which identifies the end of the batch phase. The AI system was successfully used during high cell density cultivations of recombinant Escherichia coli. The AI algorithm was validated for different systems, expressing three antigens to be used in human and animal vaccines: fragments of surface proteins of Streptococcus pneumoniae (PspA), clades 1 and 3, and of Erysipelothrix rhusiopathiae (SpaA). Standard feed-forward neural networks (NNs), with a single hidden layer, were the basis for the NNC. The NN architecture with best performance had the following inputs: stirrer speed, inlet air, and oxygen flow rates, carbon dioxide evolution rate, and CO2 molar fraction in the exhaust gas.