We led the design of advanced Animal Cell Culture Bioprocesses that have been transferred to Canadian and other industrial and non-profit organizations, novel soft and hard probes to on-line monitor changes in animal cell physiological states in real time during bioreactor culture operations. Changes in the cell physiological states provided valuable insights into the infection/production kinetics process. It also allowed the identification of key events relating to cell/virus interaction, DNA replication, virus budding on as well release from the cell surface, maximum metabolic activity and onset of lysis and death of cells, as well as accumulation of the product induced by transgene expression. For example, on-line monitoring of respiration activity in animal cell culture using advanced control strategies of dissolved oxygen, mass spectrometry and infrared analysis has been developed along with algorithms to interpret the changes in the respiration pattern during the course of the culture. Direct on-line monitoring of the biomass has been done using permittivity measurements that are an indication of the viable cell biovolume. These developments are now applied in the context of Process Analytical technologies (PAT) critical to the Quality by Design of the GMP processes and have been adopted by many of our industrial collaborators in late stage manufacturing.