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Morris Plains, NJ

The Waters Kiloprep Chromatography pilot plant is one example of the successful extension of an analytical chromatography process to the process scale. The ability to control the various operation parameters to scaleup directly from the laboratory to the pilot plant and beyond to commercial production has been developed.'1061 Figure 42 illustrates how the performance of this larger system can be predicted from the data generated in an equivalent laboratory apparatus.

Voser and Walliser'74' have described the approaches different companies have devised so that fine and soft adsorbents may be utilized in large scale chromatography operations. The scaling-up has usually been achieved by increasing the column diameter and using stack columns. The problem then becomes one of achieving uniform distribution of the feed solution over the entire resin bed surface, particularly when gradient elution is involved.

In the Pharmacia approach, the fluid input is split and distributed through six ports on the column end plates.[107] At the entrance of each stream, an anti-jetting device spread the liquid over a fine mesh net. A coarse net between the net and the end plate acts as both a support and a spacer. For the soft Sephadex gels G-50 to G-200, the maximum feasible bed height is 15 cm. Scaleup operations have used as many as six such squat columns in series. [1081 The drawbacks of this approach are the cumbersome adsorbent in the column.

In Amicon/Wright columns, the flow is distributed through a carefully designed system of radial ribs cut out of the end plate. There is a single central port with a suitable anti-jetting device to reduce and divert the high velocity of the entering stream. The adsorbent bed is covered with a sintered plate. Sintered plates are claimed to be more efficient than most nets to achieve an

Begin Injection

KILOPREP Unit Separation Piocms System

Load: ISO gm Flow Rate: 4Umin Column: (IS cm x 60 cm) x 2

(14 x PrepPAK Cartridge) k 2

Begin Injection tegmenta

PrepLC S00A

Load: tS gm Flow Rat*: SOOmVmin Column: S7 mm x 30 cm

PrepLC S00A

Load: tS gm Flow Rat*: SOOmVmin Column: S7 mm x 30 cm

Mobile Phase Sample i—i—i—i—i—i—i • S 4 3 2 t 0 Time (minj

Segment t

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