Production scale bioreactor

The upstream processing element of the manufacture of a batch of biopharmaceutical product begins with the removal of a single ampoule of the working cell bank. This vial is used to inoculate a small volume of sterile media, with subsequent incubation under appropriate conditions. This describes the growth of laboratory-scale starter cultures of the producer cell line. This starter culture is, in turn, used to inoculate a production-scale starter culture that is used to inoculate the production-scale bioreactor (Figure 5.7). The media composition and fermentation conditions required to... 

Figure 5.7 Outline of the upstream processing stages involved in the production of a single batch of product. Initially, the contents of a single ampoule of the working cell bank (a) are used to inoculate a few hundred millilitres of media (b). After growth, this laboratory-scale starter culture is used to inoculate several litres/tens of litres of media present in a small bioreactor (c). This production-scale starter culture is used to inoculate the production-scale bioreactor (d), which often contains several thousands/tens of thousands litres of media. This process is equally applicable to prokaryotic or eukaryotic-based producer cell lines, although the bioreactor design, conditions of growth, etc., will differ in these two instances...

Doran outlines several of the key parameters involved in the scale-up of a biological process from laboratory-scale shake flasks to production-scale bioreactors. In the first stage of studies a bench-top bioreactor, typically 1-2 L, is used to determine the oxygen requirements of the cells, their shear sensitivity, foaming characteristics, and any limitations that the reactor imposes on the organism. The results of these early studies enable decisions regarding operation in the batch, fed-batch, or continuous mode. A pilot-scale... 

Closterhuis NMG, Kossen NWE (1983) Dissolved oxygen concentration profiles in a production-scale bioreactor. Biotechnol Bioeng 26 546-550... 

Figure 6.56. Block diagram of the two-compartment model for oxygen transfer in a production-scale bioreactor (cf. Fig. 4.6), including parallel work for mixed zone (1) and bubble zone (2). For symbols see nomenclature. (Adapted from Oosterhuis, 1984.)...

Sieck, J.B., Cordes, X, Budach, W.E., Rhiel, M.H. et al. (2013) Development of a scale-down model of hydrodynamic stress to study the performance of an industrial CHO cell line under simulated production scale bioreactor conditions. J. Biotechnol, 164 (1), 41-49. 

Figure 18-11 a) Typical pH control in a production scale bioreactor and b) scaled-... 

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