Integration of continuous precipitation, crystallization and flocculation of recombinant proteins
March 5-10, 2017
Increased titer in biopharmaceutical production requires new strategies for economical processing. Precipitation, crystallization and flocculation are unit operation which overcomes productivity limits of chromatography and membrane technology. General engineering principles how to set up a precipitation, crystallization, or flocculation process for purification of recombinant proteins have shown in the past. The biophysical principles of precipitation by salt, organic solvent and non-ionic polymers will be explained and commonality with crystallization and flocculation discussed and it will be shown how they can be integrated into a continuous process for recovery proteins. Thermodynamic (phase diagrams)and engineering models, and kinetics of precipitation, crystallization, and flocculation (orthokinetic and perikinetic phase, induction time) have been developed for several proteins such as antibodies and interferon gamma. Scale up rules will be explained and how a process can be transferred into a continuous operation; in particular, the concept of fractal dimension (Figure 1) and the Camp number discussed.
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Alois Jungbauer, "Integration of continuous precipitation, crystallization and flocculation of recombinant proteins" in "Separations Technology IX: New Frontiers in Media, Techniques, and Technologies", Kamalesh K. Sirkar, New Jersey Institute of Technology, USA Steven M. Crame, Rensselaer Polytechnic Institute, USA João G. Crespo, LAQV-Requimte, FCT-Universidade Nova de Lisboa, Caparica, Portugal Marco Mazzotti, ETH Zurich, Switzerland Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/separations_technology_ix/41