CONTINUOUS PROCESSING: The Multicolumn Countercurrent Solvent Gradient Purification Process - A continuous chromatographic process for monoclonal antibodies without using Protein A - BioPharm


CONTINUOUS PROCESSING: The Multicolumn Countercurrent Solvent Gradient Purification Process
A continuous chromatographic process for monoclonal antibodies without using Protein A

BioPharm International

The details of this process, including the fractionation methods and the product fraction, have been explained in detail elsewhere.7 This process is ideal because it is assumed that the perfect cut of the chromatogram can always be made. Therefore, all implemented recycling strategies will lead to a less than ideal performance.

The performance parameters investigated in this work have been defined as follows:

For all three processes analyzed, it has been assumed that the feed purity is 60% and the required product purity is 90%. The columns have a comparably low separation efficiency because in industrial applications preparative resins with larger particle diameters are used. Therefore, the modeling of the columns has been performed with only 5 theoretical plates per cm of column length. For the batch column processes, one column with the dimension 30 x 0.46 cm has been assumed for the MCSGP process instead of 3 columns, each 10 x 0.46 cm, so that the resin volume in all processes is the same. Additionally, a pressure drop constraint of the chromatographic columns has been taken into account for all processes.

Figure 11. Comparison of the MCSGP process with conventional single-column technologies with respect to yield and productivity for a product purity >90%
Each process has been optimized separately, where the operation parameters, for example, column load and gradient shape, have been adjusted, so that yield and productivity are optimized for the given product purity of 90%. This optimization problem results in the Pareto curves (Figure 11).

The Pareto curve of the batch process shows that the maximum yield that can be obtained is about 97%. The curve clearly shows that an increase in the productivity has to be paid for by a lower yield (e.g., reducing the yield from 80% to 60% approximately doubles the productivity from 0.0012 to 0.0027 g/min/L). Figure 11 shows that by using the ideal recycling process, yield can be pushed to 100%. This matches the purpose of recycling (i.e., increasing the yield by re-using product-rich fractions). The ideal recycling process also can improve productivity compared to the batch process (e.g., at 85% yield by a factor of 5, from 0.00082 to 0.0042 g/min/L). Productivity increases strongly for the MCSGP process with respect to the ideal recycling process (e.g., at 95% yield by a factor of 13, from 0.0025 to 0.034 g/min/L). The recycling is assumed to be ideal, hence practical recycling strategies will result in the Pareto curves falling below the one of ideal recycling.

An increase in the productivity by a factor of 13 would result in a resin volume of the MCSGP process being 13 times smaller than for the ideal recycling process if the same amount of product is produced per unit time. This also means that 13 times more product can be purified on the same resin volume per unit time or that the same amount on the same resin volume can be purified 13 times faster.

Figure 12. Comparison of the MCSGP-process with conventional single column technologies with respect to yield and solvent requirement for a product purity > 90%
The results of Figure 11 also can be plotted in terms of the solvent requirement (Figure 12).

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