The cells used in cell culture processes are all derived from animals. Their genetic and epigenetic control circuits and their physiology have evolved to carry out the physiological functions of the tissue from which they were derived, not to sustain themselves and proliferate in in vitro culture. Cell metabolism generates waste metabolites, some of which may become toxic if allowed to accumulate to high levels. A drastic difference between a bioreactor and a human body is the absence of a metabolite-balancing mechanism. The main limiting factor for productivity in a fed-batch operation is the accumulation of metabolites and culmination of other growth inhibitory factors. A key factor in increasing the productivity of a fed-batch culture process is providing a balanced chemical environment that minimizes the production of metabolites and prolongs the time it takes for them to accumulate to inhibitory levels.