In order to be of high value in industrial bioprocess development, thermodynamic analysis ought to be able to not only predict biomass yields and kinetic growth parameters, but above all the yields and the kinetics of bioproduct synthesis. The approach discussed so far is unable to make such predictions, because it considers the living cell as a black box, differentiating only in an exceedingly formal way between catabolism and anabolism. In order to cope with the many additional degrees of freedom that exist in metabolisms able to secrete bioproducts, the black box must be opened and individual metabolic pathways and pathway options have to be thermodynamically assessed and weighed against each other. The same is true for a biomass yield prediction in cultures with a complex metabolism, such as found in animal cells. The highly complex pattern of multiple substrate take-up and secretion will never be predictable based only on a simple black-box approach with essentially one degree of freedom.