caa a22 4500 445823399 CHVBK 20180317145251.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10616-011-9368-3 doi (NATIONALLICENCE)springer-10.1007/s10616-011-9368-3 The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding [Elektronische Daten] [Weiwei Hu, Claudia Berdugo, Jeffrey Chalmers] Suspension animal cell culture is now routinely scaled up to bioreactors on the order of 10,000L, and greater, to meet commercial demand. However, the concern of the ‘shear sensitivity' of animal cells still remains, not only within the bioreactor, but also in the downstream processing. As the productivities continue to increase, titer of ~10g/L are now reported with cell densities greater than 2×107cells/mL. Such high, and potentially higher cell densities will inevitably translate to increased demand in mass transfer and mixing. In addition, achieving productivity gains in both the upstream stage and downstream processes can subject the cells to aggressive environments such as those involving hydrodynamic stresses. The perception of ‘shear sensitivity' has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation; however, as cell densities and productivities continue to increase, mass transfer requirements can exceed those imposed by these arbitrary low limits. Therefore, a better understanding of how animal cells, used to produce therapeutic products, respond to hydrodynamic forces in both qualitative and quantitative ways will allow an experimentally based, higher, "upper limit” to be created to guide the design and operation of future commercial, large scale bioreactors. With respect to downstream hydrodynamic conditions, situations have already been achieved in which practical limits with respect to hydrodynamic forces have been experienced. This review mainly focuses on publications from both the academy and industry regarding the effect of hydrodynamic forces on industrially relevant animal cells, and not on the actual scale-up of bioreactors. A summary of implications and remaining challenges will also be presented. Springer Science+Business Media B.V., 2011 Hydrodynamic forces nationallicence Animal cell culture nationallicence Agitation nationallicence Sparging nationallicence Scale up nationallicence Shear sensitivity nationallicence Hu Weiwei Cell Culture Development, Biogen Idec Inc., 5000 Davis Drive, 27709, RTP, NC, USA aut Berdugo Claudia Scientist / Research & Development, BD Biosciences, 54 Loveton Circle, 21152, Sparks, MD, USA aut Chalmers Jeffrey William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Ave., 43210, Columbus, OH, USA aut Cytotechnology Springer Netherlands 63/5(2011-10-01), 445-460 0920-9069 63:5<445 2011 63 10616 https://doi.org/10.1007/s10616-011-9368-3 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10616-011-9368-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hu Weiwei Cell Culture Development, Biogen Idec Inc., 5000 Davis Drive, 27709, RTP, NC, USA aut NATIONALLICENCE 700 1- Berdugo Claudia Scientist / Research & Development, BD Biosciences, 54 Loveton Circle, 21152, Sparks, MD, USA aut NATIONALLICENCE 700 1- Chalmers Jeffrey William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Ave., 43210, Columbus, OH, USA aut NATIONALLICENCE 773 0- Cytotechnology Springer Netherlands 63/5(2011-10-01), 445-460 0920-9069 63:5<445 2011 63 10616 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer