A scale-up from the bench to pilot scale can be on the order of 100-fold. The subsequent scale-up from pilot to production scale is generally smaller, usually no more than 25-fold. The defined (developed) process is scaled using the following general guidelines outlined in Table 1. These parameters reflect implementing a desired increase in throughput by increasing the column volume.
In general, the volume of a column is increased by making it wider and maintaining a constant bed height. By keeping the linear velocity constant, the volumetric flow rate increases and mobile phase volumes are directly proportional to the increased column volume.
There are practical caveats to following the above guidelines to the letter. A linear flow rate that can be achieved with laboratory columns may not translate to production scale columns due to lack of mechanical support from the column wall. Efforts to maintain the same flow rate may result in a prohibitive pressure drop. For this reason, it is recommended, where possible, that final optimization of flow rate be done at a scale employing columns that are 10 cm in diameter.
Table 1 Guidelines for Scale-up of Chromatographic Process
Kept constant Increased
Resin bed height Column diameter
Linear velocity of mobile phase Volumetric flow rate
Sample concentration Sample and mobile phase volumes
Gradient slope Gradient volume
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