Evaluation of selected control strategies for fed-batch cultures of a hybridoma cell line.
While fed-batch suspension culture of animal cells continues to be of industrial importance for the large-scale production of pharmaceutical products, existing control concepts are still insufficient. The present paper illustrates the advantages and disadvantages of different fed-batch strategies, including fixed-feed trajectories, control via OUR (oxygen uptake rate) (stoichiometric feeding), a priori determination of feed trajectories based on a kinetic model and the model-based adaptive OLFO (open-loop-feedback-optimal) control strategy. A recommendation as to which control strategy should be used for a specific process has to consider the respective process. For an established process with a well characterized and stable production cell line, probably the application of a fixed feed trajectory should be recommended. An adaptive, model-based control strategy could be the method of choice during cell-line development or for rapid production of small amounts of product for clinical trials, owing to its universal character and because it does not require intensive process development.
Pörtner
Ralf
R
Technische Universität Hamburg-Harburg, Bioprozess-und Bioverfahrenstechnik, Denickestr. 15, 21071 Hamburg, Germany. poertner@tuhh.de
Schwabe
Jan-Oliver
JO
Frahm
Björn
B
D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002470:Cell Survival; D003198:Computer Simulation; D005246:Feedback / Q000502:physiology*; D006825:Hybridomas / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013673:Technology Assessment, Biomedical
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins