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.
Technische Universität Hamburg-Harburg, Bioprozess-und Bioverfahrenstechnik, Denickestr. 15, 21071 Hamburg, Germany. poertner@tuhh.de
Ralf
R
Pörtner
Jan-Oliver
JO
Schwabe
Björn
B
Frahm
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