Biomedical Engineering Reference
In-Depth Information
6 Conclusions
This chapter has reviewed a range of resource-efficient methods for the extreme
scale-down development of chromatographic separations along with selected case
study examples. Such methods allow engineers to obtain information early in
development about how a large-scale process could perform. The outcome of a
scale-down device can be either information about general trends across a search
space or the provision of more accurate information for predicting scale-up per-
formance. Direct scale-up prediction will require knowledge of the large-scale
engineering environment to be replicated satisfactorily in the small devices. This
may be possible by direct calibration of the scale-down devices, or it may also
need the use of mathematical modelling to adjust scale-down outputs. Of addi-
tional importance are the principles of parallelisation and automation, which
increase throughput significantly and thus allow many more options to be con-
sidered than might otherwise be the case. This increases process confidence and
understanding and allows a rational basis for choosing a specific process design,
thus enabling efficient and cost-effective column development.
References
1. Bensch M, Wierling PS, von Lieres E, Hubbuch J (2005) High throughput screening of
chromatographic phases for rapid process development. Chem Eng Technol 28:1274-1284
2. Bergander T, Nilsson-Välimaa K, Öberg K, Ł˛cki KM (2008) High-throughput process
development: determination of dynamic binding capacity using microtiter filter plates filled
with chromatography resin. Biotechnol Progr 24:632-639
3. Bhambure R, Kumar K, Rathore AS (2011) High-throughput process development for
biopharmaceutical drug substances. Trends Biotechnol 29:127-135
4. Charlton H, Galarza B, Leriche K, Jones R (2006) Chromatography process development using
96-well microplate formats. Biopharm Int.
http://biopharminternational.findpharma.com
5. Chhatre S, Francis R, Bracewell DG, Titchener-Hooker NJ (2010) An automated packed
Protein G micro-pipette tip assay for rapid quantification of polyclonal antibodies in ovine
serum. J Chromatogr B 878:3067-3075
6. Chhatre S, Konstantinidis S, Ji Y, Edwards-Parton S, Zhou Y, Titchener-Hooker NJ (2011)
The simplex algorithm for the rapid identification of operating conditions during early
bioprocess development: case studies in FAb' precipitation and multimodal chromatography.
Biotechnol Bioeng 108:2162-2170
7. Coffman JL, Kramarczyk JF, Kelley BD (2008a) High-throughput screening of chromatographic
separations: I. Method development and column modeling. Biotechnol Bioeng 100:605-618
8. Dismer F, Petzold M, Hubbuch J (2008) Effects of ionic strength and mobile phase pH on the
binding orientation of lysozyme on different ion-exchange adsorbents. J Chromatogr A
1194:11-21
9. Gerontas S, Asplund M, Hjorth R, Bracewell DG (2010) Integration of scale-down
experimentation and general rate modelling to predict manufacturing scale chromatographic
separations. J Chromatogr A 1217:6917-6926
10. Herrmann T, Schroder M, Hubbuch J (2006) Generation of equally sized particle plaques
using solid-liquid suspensions. Biotechnol Progr 22:914-918
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