Hybridoma cells utilize a pair of complementary and partially substitutable substrates, glucose and glutamine, for growth. It has been shown that cellular metabolism shifts under different culture conditions. When those cultures at different metabolic states are switched to a continuous mode, they reach different steady states under the same operating conditions. A cybernetic model was constructed to describe the complementary and partial substitutable nature of substrate utilization. The model successfully predicted the metabolic shift and multiple steady-state behavior. The results are consistent with the experimental observation that the history of the culture affects the resulting steady state.

Mammalian cells are widely used in the production of viral vaccines and therapeutic proteins. Most of those processes employ cells growing in suspension; however, some, especially those in vaccine production, use adherent cells. Stirred‐tank bioreactors are most widely used for mammalian cell culture processes. When a stirred‐tank bioreactor is used for growing adherent cells, a supporting surface for cell attachment is provided by the use of microcarriers or macroporous microcarriers. Alternatively, adherent cells are grown as aggregates in suspension. Fed‐batch culture is commonly practised since it reaches high cell and product concentrations. When a stirred‐tank bioreactor is operated in a continuous mode, it is a common practice to employ a cell retention device for perfusion in order to increase cell and product concentrations. As mammalian cell culture processes are increasingly being used in the manufacturing, one also witnesses an increasing adoption of disposable (or single‐use) cell culture devices. Traditional roller bottles are still often seen. Additionally, multiple flat plates or parallel trays, along with bag type cell growth chambers and even plastic stirred tanks, are used in moderate‐scale production and in the seed culture propagation for large‐scale bioreactors. Those disposable devices offer simplicity in operations and ease process validation in the production of biopharmaceuticals. Recently, some innovative bioreactors developed nearly two decades ago are finding applications in tissue engineering. Furthermore, the demand for high throughput operations in cell culture processing will continue to drive the innovations in bioreactor technology.

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