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Comparison of different options for harvest of a therapeutic protein product from high cell density yeast fermentation broth
Author(s) -
Wang Alice,
Lewus Rachael,
Rathore Anurag S.
Publication year - 2006
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20816
Subject(s) - microfiltration , yeast , centrifugation , fermentation , filtration (mathematics) , chromatography , cross flow filtration , diafiltration , process engineering , pulp and paper industry , chemistry , food science , mathematics , membrane , engineering , biochemistry , statistics
Recovery of therapeutic protein from high cell density yeast fermentations at commercial scale is a challenging task. In this study, we investigate and compare three different harvest approaches, namely centrifugation followed by depth filtration, centrifugation followed by filter‐aid enhanced depth filtration, and microfiltration. This is achieved by presenting a case study involving recovery of a therapeutic protein from Pichia pastoris fermentation broth. The focus of this study is on performance of the depth filtration and the microfiltration steps. The experimental data has been fitted to the conventional models for cake filtration to evaluate specific cake resistance and cake compressibility. In the case of microfiltration, the experimental data agrees well with flux predicted by shear induced diffusion model. It is shown that, under optimal conditions, all three options can deliver the desired product recovery ( >80%), harvest time ( <15 h including sequential concentration/diafiltration step), and clarification ( <6 NTU). However, the three options differ in terms of process development time required, capital cost, consumable cost, ease of scale‐ability and process robustness. It is recommended that these be kept under consideration when making a final decision on a harvesting approach. © 2006 Wiley Periodicals, Inc.