Automated System and Method for Monitoring Chromatography Column Performance, and Applications Thereof

Abstract

The present invention provides automated systems and methods for monitoring column performance in process chromatography, and applications thereof. In an embodiment, column performance is monitored by generating a plurality of process values such as, for example, conductivity values or pH values with a detector during a chromatography step transition between a first mobile phase liquid and a second mobile phase liquid. The process values are transformed to form transformed process values in which noise present in the process values is suppressed. Column performance parameters are calculated based on the transformed process values and displayed during movement of the second mobile phase liquid through the chromatography column. The displayed performance parameters enable an operator to make a determination, for example, regarding the quality of the chromatography column packing and whether to continue the chromatography process or stop the chromatography process until the chromatography column can be repacked or replaced.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of allowed U.S. Non-Provisional application Ser. No. 12 / 863,955, having a §371(c) date of Mar. 10, 2011, which is a national stage application of PCT Application No. PCT / US09 / 00469, filed Jan. 23, 2009, which claims the benefit of U.S. Provisional Application No. 61 / 023,747, filed Jan. 25, 2008, all of which are incorporated herein by reference in their entireties.BACKGROUND OF THE PRESENT INVENTION[0002]In the biopharmaceutical industry, process chromatography using packed-bed columns is a key component in the manufacture of complex biological products. In order to ensure product quality and performance (e.g., biological activity), a high packing quality is required. Accordingly, packing quality must be monitored and packed-bed columns having an unacceptable packing quality must be repacked or replaced.[0003]Conventionally, three numeric parameters, namely, the number of plates per column (N), height equi...

AI Technical Summary

Benefits of technology

The present invention allows for a direct measure of how well a chromatography column is working while the column is in use to make certain products. This can be done without stopping or delaying the production process.

Problems solved by technology

Accordingly, packing quality must be monitored and packed-bed columns having an unacceptable packing quality must be repacked or replaced.

Because there are frequently situations where the peaks from pulse injection experiments or HETP runs are not Gaussian, the N, HETP, and As values calculated in accordance with the pulse injection method often do not accurately describe the efficiency or packing quality of a column.

This is especially true for large process chromatography columns, which routinely give peaks that do not fit a Gaussian distribution.

For the same reason, the pulse injection method is not robust because noise occurring at these critical points will be weighted heavily and lead to incorrect calculations.

In addition to the above noted shortcomings, there are also practical and economical reasons that make the pulse injection method for determining packing quality poorly suited for use in large-scale process chromatography.

Since it is difficult to accurately introduce a small pulse into a large column, the reproducibility of HETP runs at the production scale is typically low, especially where subtle changes in the column are concerned.

This weakness can render the parameters measured with the pulse injection method unsuitable for use with statistical process control.

Furthermore, HETP runs are external to the manufacturing process, and the parameters derived from them are not direct measures of the efficiency or packing quality of the columns when the columns are actually used during the manufacturing process.

When the change is sufficiently large, it can have potentially catastrophic effects on the ensuing process chromatography.

These HETP runs consume process resources and can cause delays in production.

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