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Principles
For successful transfer of chromatography unit operations a few basic rules can be followed.
Anything that relates to the chromatographic performance should be kept constant upon scale up whenever possible to ensure conformity in performance between laboratory scale and final production scale. If scalability has been considered from beginning of process development, the actual scale up of a chromatography step should be very straight forward, basically involving only an increase of the diameter of the chromatography column to accommodate the larger feed volume at preserved processing time.
When using long beds, such as in size exclusion chromatography, it may sometimes be recommended to stack the column in several shorter segments connected in series in order to reduce the drag force on the beads in the column when wall support decreases at larger column diameters. This will facilitate higher flow velocity at large scale.
Parameters to be maintained during scale up:
- Bed height
- Flow velocity (cm/h)
- Length of eluting step(s)/media volume
- Gradient volume/media volume
- Sample concentration and composition
- Sample volume/media volume
Parameters to be increased during scale up:
- Column diameter
- Volumetric flow rate (L/h)
- Sample volume proportionally
- Equilibration, washing and elution volume proportionally
- Gradient volume proportionally
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