Methods and strategies available for the process control and optimization of monoclonal antibody production.
The objective of this paper is to explore the range of methods and strategies available for the process control and optimization of monoclonal antibody production by hybridoma cell culture. Emphasis will be placed on the choice of the level of complexity incorporated into the process control and optimisation procedure. It will be shown that the behaviour of hybridomas in culture is influenced by sophisticated cellular metabolic activities and various interactive environmental factors and that the understanding and modelling of the way hybridomas grow in the bioreactor should enable optimisation of bioreactor operating conditions to achieve maximum monoclonal antibody formation. However, due to the lack of on-line instrumentation of important biological variables and the incomplete knowledge of hybridoma cultivation process, there exist many limitations and challenges to the advent of applications of process control and optimisation in this field. To solve the problem, introduction of industrially practical biological measurements and development of new control concepts are inevitable. At the end of this paper, we shall discuss possible schemes for the control of the physiological state of cells in order that balanced cell growth and maximum monoclonal antibody synthesis may be achieved.
Fu
P
P
Chemical Engineering Department, Sydney University, NSW, Australia.
Barford
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001709:Biotechnology / Q000379:methods*; D006825:Hybridomas / Q000378:metabolism*
D000911:Antibodies, Monoclonal