Extreme Scale-Down Approaches for Rapid Chromatography Column Design and Scale-Up During Bioprocess Development - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 109

Extreme Scale-Down Approaches
for Rapid Chromatography Column
Design and Scale-Up During Bioprocess
Development

Sunil Chhatre

Abstract Chromatography is a ubiquitous protein purification step owing to its
unparalleled ability to recover and purify molecules from highly complex indus-
trial feedstocks. Traditionally, column development has been driven by a combi-
nation of prior experience and empirical studies in order to make the best choices
for design variables. Economic constraints now demand that companies engage
with a more systematic exploration of a chromatographic design space. To deliver
this capability using purely conventional laboratory columns, however, would
require considerable resources to identify practical and economical operating
protocols. Hence, recently there has been increased use of extremely small-scale
devices that gather data quickly and with minimal feed requirements. Such
information can be obtained either during early development for screening and
trend-finding purposes or later for more accurate scale-up prediction. This chapter
describes some of the key drivers for these small-scale studies and the different
types of extreme scale-down chromatography formats that exist and illustrates
their use through published case studies. Since extreme scale-down experimen-
tation is linked to fundamental mechanistic engineering approaches as well, the
utility of these in delivering process understanding is also highlighted.

Keywords Batch incubation Extreme scale-down High-throughput screening
Miniature columns Pipette tips

Contents

1 Introduction........................................................................................................................ 110

2 General Considerations for Extreme Scale-Down ........................................................... 111

3 Millilitre Scale-Down ........................................................................................................ 113

S. Chhatre ( )

The Advanced Centre for Biochemical Engineering, University College London,
Gower Street, London WC1E 7JE, UK
e-mail: [e-mail]

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