Methods and systems for chromatography data analysis

Patent metadata

Field	Value
Publication number	US-11333642-B2
Application number	US-202016797548-A
Country	US
Kind code	B2
Filing date	Feb 21, 2020
Priority date	Oct 25, 2016
Publication date	May 17, 2022
Grant date	May 17, 2022

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:
receiving raw chromatography data including a plurality of signals and a plurality of blocks;
processing the raw chromatography data by selecting a combination of a first block and a first signal from the raw chromatography data;
performing a transition analysis on the processed raw chromatography data, wherein performing the transition analysis includes:
generating performance parameters, the performance parameters including a maximum rate of change or a number of inflection points; and
based on the performance parameters, generating the transition data;

generating an Individual chart, a Moving Range chart, or a Range chart based on the transition data; and
generating performance data by applying a statistical process control to the Individual chart, Moving Range chart, or Range chart.

2. The process of claim 1 , further comprising performing an action based on the performance data, wherein the action comprises at least one of:
generating a notification of an event;
generating an evaluation of the event; or
generating a deviation notification form.

3. The method of claim 1 , further comprising performing a chromatography column run and generating raw chromatography data from the chromatography column run;
wherein the raw chromatography data is used to generate the processed chromatography data.

4. The method of claim 3 , wherein the raw chromatography data includes a plurality of signals, and 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.

5. The method of claim 3 , further comprising:
generating smoothed data by applying a 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.

6. The method of claim 5 , further comprising:
generating the processed chromatography data by selecting smoothed data matching a feature of a chromatogram transition.

7. The method of claim 5 , wherein performing the noise reduction technique includes:
selecting a portion of the raw chromatography data to analyze using predetermined set points;
using at least one smoothing filter on the selected portion of data to generate smoothed data;
normalizing the selected portion of data to prevent magnitude bias; and
analyzing the selected portion of data for dynamic signal errors.

8. The method of claim 1 , wherein the transition analysis further includes:
generating a curve using the processed chromatography data; and
analyzing the curve to generate performances parameters.

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

generating processed chromatography data by selecting smoothed data matching a feature of a chromatogram transition, wherein the feature of the chromatogram transition includes:
a derivative duration;
a maximum intensity;
a duration from initiation; or
expected background noise; and

using the processed chromatography data to generate one of an Individual chart, a Moving Range chart, or a Range chart.

10. The method of claim 9 , wherein the noise reduction technique further comprises:
normalizing the portion of raw chromatography data to prevent magnitude bias;
analyzing the portion of raw chromatography data for dynamic signal errors; or
both.

11. The method of claim 9 , further comprising:
generating performance data by applying a statistical process control to the Individual chart, Moving Range chart, or Range chart by:
performing a multivariate data analysis; or
performing a principal component analysis.

12. The method of claim 11 , further comprising:
performing an action based on the performance data, wherein the action comprises at least one of:
generating a notification of an event;
generating an evaluation of the event; or
generating a deviation notification form.

13. The method of claim 9 , wherein the selection of raw chromatography data is received from a chromatography process skid.

14. The method of claim 9 , further comprising:
performing a transition analysis on the processed chromatography data to generate transition data, wherein performing the transition analysis includes:
generating performance parameters, the performance parameters including a maximum rate of change or a number of inflection points; and
based on the performance parameters, generating the 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.

15. The method of claim 9 , further comprising:
performing a transition analysis to generate transition data, wherein performing a transition analysis includes:
generating a curve using the processed chromatography data;
analyzing the curve to generate performance parameters; and
based on the performance parameters, generating the 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.

16. A process control method, comprising:
receiving raw chromatography data including a plurality of signals, wherein each signal of the plurality of signals is associated with one of a plurality of blocks;
generating processed chromatography data by applying a noise reduction technique to a subset of the raw chromatography data, wherein applying the noise reduction technique includes:
selecting a portion of the subset of the raw chromatography data to analyze using predetermined set points; and
using at least one smoothing filter on the portion to generate smoothed data;

generating performance parameters, the performance parameters including a maximum rate of change or a number of inflection points;
based on the performance parameters, generating the 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.

17. The method of claim 16 , further comprising:
performing a chromatography column run, wherein the raw chromatography data is received from the chromatography column run.

18. The method of claim 16 , wherein each block of the plurality of blocks corresponds to a step in a chromatography process.

19. The method of claim 16 , further comprising:
selecting the combination of the first block and the first signal according to a profile defining a plurality of selection criteria, wherein the plurality of selection criteria comprises:
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 variat

Assignees

• Regeneron Pharma
• Regeneran Pharmaceuticals Inc

Inventors

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

Classifications

• 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

• G01N30/8693 Primary

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

• G01N30/8617

  Filtering, e.g. Fourier filtering · CPC title