Strategies Used in Manufacturing Processes to Drive and Control Mammalian Cells to Undergo a Lactate Metabolic Shift

Author(s): Naveenganesh Muralidharan, Emma Bolduc, Mark Davis

Mammalian cells used in the production of biologics frequently switch from glucose to lactate as a source of energy, a process known as a lactate metabolic shift. While this response is desirable because it leads to high yields, it does not occur spontaneously nor is it well understood. Even in highly controlled commercial manufacturing facilities, some batches undergo a lactate metabolic shift while others do not. Here we review our current understanding of the bioreactor operating parameters that may have an impact on the lactate metabolic shift, including pH, pCO2, and glucose and lactate together with conditions used for media preparation, filtration, batching, and equilibration. The information presented might be used to troubleshoot problems leading to inconsistent lactate metabolic shifts and the development of more effective control strategies.