Modelling Approaches for Bio-Manufacturing Operations - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 104

process constraints, these can provide numerical understanding of where to
operate. Windows are shown conventionally as a series of two-dimensional maps;
three-dimensional windows can also be used and are defined by an operating
volume by plotting three variables on each of three axes [ 22 ]. Ultimately, such
information can enable the definition of suitable operating protocols. In one
example for chromatography, windows of operation were used by Boushaba et al.
[ 3 ], in which the general rate model was calibrated using experimental break-
through curves from feedstocks generated at variable levels of centrifugal pre-
clarification. The calibrated model was then used to plot windows of operation that
related the input load volume and flow rate to the yield and throughput. The results
showed how the size and position of the feasible load volume-flow rate operating
window changed as the clarification efficiency of the preceding centrifuge was
altered.
6 Conclusions
This chapter has sought to evaluate some of the modelling approaches used in the
bioprocessing sector to evaluate the technical and economic performance of both
individual unit operations and also process flowsheets. Modelling methods have
the potential to augment development approaches by enabling the rapid, cost-
effective evaluation of process options. To achieve this however requires access to
suitable modelling equations and adequate amounts of data or use of sensible
assumptions to deliver relevant, accurate predictions of the technical and economic
performance of a manufacturing process or facility. Aside from issues of yield,
purity or cost of goods, other important aspects addressed by models include
scheduling, facility fit and wider strategic issues which determine how best to
enhance the development and manufacturing platforms of a company. Modelling
frameworks need to be seen in the context of other approaches such as microscale
methods ( Chap. 7 ) and rapid analytical techniques that form a portfolio of tech-
nologies developed in the last decade for accelerating the design, development and
optimisation of biopharmaceutical production operations.
References
1. Ambler CM (1959) The theory of scaling up laboratory data for the sedimentation type
centrifuge. J Biochem Microbiol Technol Eng 1:185-205
2. Boulding N, Yim SSS, Keshavarz-Moore E, Ayazi Shamlou P, Berry M (2002) Ultra
scaledown to predict filtering centrifugation of secreted antibody fragments from fungal
broth. Biotechnol Bioeng 79:381-388
3. Boushaba R, Baldascini H, Gerontas S, Titchener-Hooker NJ, Bracewell DG (2011)
Demonstration of the use of windows of operation to visualize the effects of fouling on the
performance of a chromatographic step. Biotechnol Progr 27:1009-1017