Scale-up engineering in animal cell technology: Part I

Abstract

‘Scale-up’ is sometimes loosely used to describe an increase in production capacity. The purpose of any scale-up procedure is to reproduce a given process on a larger scale and to achieve a predictable process result. Scale-up may, therefore, be defined as the ‘predictable’ (engineered) increase in production capacity. Ideally, what the scale-up engineer would like to do is simulate and predict the performance of a large-scale reactor (e.g. 5000 l reactor volume) using only data from a bench-top vessel (e.g. 5 l volume). In order to do this equations are required that correlate the performance of a reactor with its size. In this review we will address some of the current trends and approaches currently being pursued to establish the basis for such calculations. Most of the correlations in animal cell culture processes are based on laboratory models alone, and still await confirmation of their utility as practical industrial tools. Although development work of this kind is under way within the industry, commercial constraints impede publication. Neither the validity of the theoretical concepts underlying these models nor the various possible reactor designs will be reviewed. Rather we will address the approaches to establishing the numerical tools needed to determine the required reactor design, its subsequent optimization, scale-up and scale-down procedures.