Using Volumetric Flow to Scaleup Chromatographic Processes - - BioPharm International


Using Volumetric Flow to Scaleup Chromatographic Processes

BioPharm International
Volume 19, Issue 3

An entirely different scaleup example is shown in Figure 8. Delay volume causes the difference in retention volumes. The compressed shape of the lab profile is due to UV-detector saturation. In Figure 9 the profiles are compared, corrected for Δ delay volume thereby confirming this method.

Figure 9. Profiles from Fig. 8 corrected for D delay volumes. Note that the profiles do not match completely due to the better performance (slightly narrower main peak and better separated peaks) in pilot scale as predicted by the increased number of plates.


In order to predict and correct for differences in retention volumes when scaling up a particular process from lab to pilot and production scale a table of Δ delay volumes for the process in all three systems was constructed. The results are shown in Table 1, which also contains the dead volumes for comparison.

Table 1. Sample table of delay volumes (for the relevant gradient). Retention differences can be predicted and corrected for during scaling up (or down) by applying the D delay volume. The table could be used to directly transfer a process between lab and production.

We have shown that it is possible to scale up the chromatographic process at constant productivity while changing both the bed height and the diameter. In both experimental cases identical impurity profiles were found at scale up. The differences in retention volumes observed during process transfer from lab to pilot could be accounted for by extra column effects. This requires using the delay volume from the relevant gradient (and not just the dead volume) for correction.


We would like to thank Ernst Hansen (Novozymes) for scientific discussions and review and Lars Sejergaard (Novo Nordisk) for collaboration with ideas and experiments.

Steffen Kidal is a research scientist, 201 BioProcess Purification at Novo Nordisk A/S (Brudelysvej 20, DK-2880 Bagsvœrd, Denmark, 45.4443.2545,

Ole Elvang Jensen is principal scientist, 427 Purification Plants at Novo Nordisk A/S (Hagedornsvej 1, DK-2820 Gentofte, Denmark, 45.4443.9279,

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