title: Verification of energy dissipation rate scalability in pilot and production scale bioreactors using computational fluid dynamics.
abstract: Suspension mammalian cell cultures in aerated stirred tank bioreactors are widely used in the production of monoclonal antibodies. Given that production scale cell culture operations are typically performed in very large bioreactors (≥ 10,000 L), bioreactor scale-down and scale-up become crucial in the development of robust cell-culture processes. For successful scale-up and scale-down of cell culture operations, it is important to understand the scale-dependence of the distribution of the energy dissipation rates in a bioreactor. Computational fluid dynamics (CFD) simulations can provide an additional layer of depth to bioreactor scalability analysis. In this communication, we use CFD analyses of five bioreactor configurations to evaluate energy dissipation rates and Kolmogorov length scale distributions at various scales. The results show that hydrodynamic scalability is achievable as long as major design features (# of baffles, impellers) remain consistent across the scales. Finally, in all configurations, the mean Kolmogorov length scale is substantially higher than the average cell size, indicating that catastrophic cell damage due to mechanical agitation is highly unlikely at all scales.
authors.affiliation: Global Engineering Sciences, Biogen Idec Inc., 10 Cambridge Center, Cambridge, MA, 02142.
authors.forename: Chris
authors.initials: C
authors.lastname: Johnson
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Natarajan
authors.forename: Chris
authors.initials: C
authors.lastname: Antoniou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods; D003198:Computer Simulation; D057446:Hydrodynamics
chemical_list: D000911:Antibodies, Monoclonal
keywords: CFD; Kolmogorov length scales; antibodies; bioreactors; energy dissipation rates; scalability