Modern biotechnology industries, such as those producing biopharmaceuticals, are heavily reliant upon upstream bioprocessing in which micro-organisms and cells are used as biochemical factories. A fed-batch process is commonly used for feeding organisms at the conditions required for optimum production due to its simplicity and flexibility of use with a wide range of organisms and associated products. In an ideal fed-batch process the culture is supplied with nutrients, at a rate which matches their consumption, such that detrimental excess or depletion is never experienced. Due to operational limitations, this is rarely achieved in practice as most operators employ fixed, scheduled feeding strategies with control through off line assays. Feed on-demand strategies, as described here, offer the potential for rapidly determining fixed feeding schedules during process development and for implementation of closed-loop nutrient control during scale-up and production
The use of Metabolic Rate Index for closed loop control of feeding in Mammalian Cell Culture bioprocesses.