Methods and systems for chromatography data analysis

Patent metadata

Field	Value
Publication number	US-11680930-B2
Application number	US-202217659526-A
Country	US
Kind code	B2
Filing date	Apr 18, 2022
Priority date	Oct 25, 2016
Publication date	Jun 20, 2023
Grant date	Jun 20, 2023

Abstract

Embodiments of the present disclosure are directed to methods and systems for assessing integrity of chromatography columns, systems, and processes. The methods and systems can comprise one or more of extracting a block and signal combination for analysis, performing a transition analysis, performing one or more statistical process controls, and/or implementing in-process controls based on the statistical process controls.

First claim

What is claimed is:

1. A process control method, comprising:
generating smoothed data by applying a noise reduction technique to raw chromatography data, wherein the noise reduction technique comprises using a smoothing filter on a portion of raw chromatography data to generate smoothed data;
generating processed chromatography data by selecting smoothed data matching a feature of a chromatogram transition;
performing a transition analysis to generate transition data; and
performing an action based on the transition data, wherein performing the action includes generating a notification of an event, generating an evaluation of the event, or generating a deviation notification form.

2. The method of claim 1 , wherein the feature of the chromatogram transition includes:
a derivative duration;
a maximum intensity;
a duration from initiation; or
expected background noise.

3. The method of claim 1 , wherein the noise reduction technique further includes selecting the portion of the raw chromatography data using predetermined set points.

4. The method of claim 1 , wherein the noise reduction technique further includes:
analyzing the portion of raw chromatography data for dynamic signal errors;
normalizing the portion of raw chromatography data to prevent magnitude bias; or both.

5. The method of claim 1 , wherein performing the transition analysis includes:
generating a performance parameter based on the processed chromatography data, the performance parameter including a maximum rate of change, a number of inflection points, a breakthrough volume, a cumulative error, a curve asymmetry, or a combination thereof; and
generating transition data based on the performance parameter or generating transition data based on the performance parameter in combination with historical data.

6. The method of claim 1 , wherein performing a transition analysis includes:
generating a curve using the processed chromatography data;
analyzing the curve to generate a performance parameter; and
generating the transition data based on the performance parameter.

7. A process control method, comprising:
processing raw chromatography data including a plurality of signals and a plurality of blocks, to generate processed raw chromatography data by applying a noise reduction technique to the plurality of signals and the plurality of blocks;
performing a transition analysis on the processed raw chromatography data, to generate transition data, wherein performing the transition analysis includes:
generating a curve using the processed chromatography data;
analyzing the curve to generate a performance parameter; and
generating the transition data based on the performance parameter; and

performing an action based on the transition data, wherein performing the action includes generating a notification of an event, generating an evaluation of the event, or generating a deviation notification form.

8. The method of claim 7 , further comprising:
generating an Individual chart, Moving Range chart, or Range chart; and
applying a statistical process control to the Individual chart, Moving Range chart, or Range chart, to generate performance data.

9. The method of claim 8 , wherein performing the action based on the transition data includes performing the action based on the transition data and the performance data.

10. The method of claim 7 , wherein each signal of the plurality of signals is associated with one of a plurality of blocks, and
wherein each block of the plurality of blocks corresponds to a step in the chromatography column run.

11. The method of claim 7 , wherein processing raw chromatography data includes selecting a combination of a first block and a first signal from the raw chromatography data.

12. The method of claim 11 , wherein selecting the combination of the first block and the first signal includes selecting the combination according to a profile defining a plurality of selection criteria, wherein the plurality of selection criteria comprises one or more of:
whether blocks occur at regular chromatography cycle intervals;
an extent to which one of the plurality of signals saturates a detector;
an extent to which the plurality of signals approaches a stationary phase at a distinct level;
a magnitude of variation in the plurality of signals; and
a number of inflection points shown by the plurality of signals during a transition phase.

13. The method of claim 7 , wherein the performance parameter includes two or more of:
a maximum rate of change;
a number of inflection points;
a breakthrough volume;
a cumulative error;
a curve asymmetry; and
a height equivalent of a theoretical plate.

14. The method of claim 7 , further comprising performing a chromatography column run and generating the raw chromatography data from the chromatography column run.

15. The method of claim 14 , wherein the transition data is indicative of an integrity of a chromatography column used in the chromatography column run.

16. The method of claim 7 , further comprising:
generating smoothed data by applying the noise reduction technique to a selection of the raw chromatography data, wherein the noise reduction technique increases a signal-to-noise ratio of the selection of the raw chromatography data; and
processing raw chromatography data includes processing the smoothed data.

17. A process control method, comprising:
generating smoothed data by applying a noise reduction technique to raw chromatography data, wherein the noise reduction technique comprises:
selecting a portion of raw chromatography data using predetermined set points; and
using a smoothing filter on the portion of raw chromatography data to generate smoothed data;

generating a performance parameter based on the smoothed data, wherein the performance parameter includes:
a maximum rate of change;
a number of inflection points;
a breakthrough volume;
a cumulative error;
a curve asymmetry;
a height equivalent of a theoretical plate; or
a combination thereof;

generating transition data based on the performance parameter; and
performing an action based on the transition data, wherein performing an action includes generating a notification of an event, generating an evaluation of the event, or generating a deviation notification form.

18. The method of claim 17 , wherein the noise reduction technique further comprises normalizing the selected portion of data to prevent magnitude bias and analyzing the selected portion of data for dynamic signal errors.

19. The method of claim 17 , further comprising:
performing a chromatography column run, wherein the raw chromatography data is generated during the chromatography column run; and
wherein the transition data is indicative of an integrity of a chromatography column used in the chromatography column run.

20. The method of claim 17 , wherein generating the performance parameter includes:
generating a curve using the smoothed data; and
analyzing the curve to generate the performance parameter.

Assignees

• Regeneron Pharma

Inventors

• Mao Nathan L
• Shierly Eric
• Schilling Bernhard
• Carver Scott
• Mcdermott Stefanie
• Mattila John
• Bak Hanne

Classifications

• G01N30/8617

  Filtering, e.g. Fourier filtering · CPC title

• G01N30/8693 Primary

  Models, e.g. prediction of retention times, method development and validation · CPC title

• G01N2030/889

  monitoring the quality of the stationary phase; column performance · CPC title

• G01N30/88 Primary

  Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 · CPC title