Scaling-Down Studies

Deshpande et al. (1992) studied scaling-down of EBRs reducing the length of reactors and ensuring identical hydrodynamic properties in commercial and laboratory units. In order to maintain a given space velocity and to reduce the reactor length, the liquid velocity has to be reduced. To achieve ebullation at this reduced liquid velocity, the particle size has to be reduced as well. The reduction in superficial liquid velocity and particle size has to be achieved in such a manner that the important hydrodynamic parameters, such as the phase holdups, remain unchanged. 

The proposed steps for reactor hydrodynamic scale-down are as follows  

Reduce U, which results in an increase in solid holdup 8j. 

Adjust the other system parameters to obtain the same liquid 8, and gas 8 holdups in both reactors. 

The adjusted parameters considered were dp, Ui, and Ug. The results obtained are presented in Table 10.6. The larger diameter particle represents the commercial unit and the smaller diameter particle the laboratory unit. The phase holdups were calculated using the generalized wake model given by the following equations (Bhatia and Epstein, 1974)  

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Chromatography steps for purification of monoclonal antibody produced by CHO cells Scale-down studies for resin use and viral clearance fully predictive of larger scale [26] (Genentech)... 

Scale-down studies have been used for a wide variety of process validation studies, including resin lifetimes, in-process stream hold times, buffer stability, virus clearance, harvest criteria, filter extractables, resin leachables, and cell age at harvest [14, 91, 92]. The ease of scale-down differs depending on step and should be considered in selecting those steps to be validated [5]. In fact, certain validation issues can be addressed only via small-scale models (e.g., virus clearance evaluation, nucleic acid and other impurities/additives removal, cleaning and storage procedure evaluation, and column lifetime estimation) because their use increases worker safety, reduces costs, and permits use of higher titer samples for improved... 

Scale-down studies are a valuable tool in fermentation development [51]. If production is going to occur in a fermentor for which the KLa or other parameter is precisely defined [52], correct down-scaled reactors should be used to mimic such configurations. Scale-down studies are helpful in that restrictions due to scale up are known in advance, thus minimizing small-scale studies that do not satisfy the ultimate good. 

Levison PR, Sweater M, and Dennis JW (1999) A scale-down study into the chromatography of a peptide using the cation-exchange cellulose Express-Ion C. Journal of Chemical Technology and Biotechnology 74 204—207. 

As the second example, the scale-down study performed by Oosterhuis [11] is summarized. Table 2.2 lists characteristic times based on estimations for a 25 m STR equipped with two standard Rushton impellers used for gluconic acid production. In this example, the time constant for oxygen transfer (Iqt) longer than that for oxygen consumption (loc)> therefore oxygen limitation is... 

The calculation of metabolic fluxes based on isotopomer distribution has gained importance as a quantitative and reliable tool for the study of cellular physiology. Metabolic fluxes are mainly calculated during steady-state conditions, which limits their applicability to scale-down dynamic studies. Nevertheless, research efforts with labeling experiments and mathematical models have allowed important advances in the dynamic C-based metabolic flux analysis [37-39], from which scale-down studies would be much benefited. An interesting example... 

Improvements Based on Scale-Down Studies Bioreactor Design and Cell Engineering... 

Nienow, A.W., Scotta, W.H., Hewitt, C.J., Thomas, C.R. et al. (2013) Scale-down studies for assessing the impact of different stress parameters on growth and product quality during animal cell culture. Chem. Eng. Res. 

Required Characteristics of a Model Culture for Scale-down Studies... 

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