Methods and systems for chromatography data analysis

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.

1 - 22 . (canceled) 
     
     
         23 . A process control method, comprising:
 receiving raw data from a detector, wherein the raw data includes a plurality of signals and plurality of blocks, and wherein the raw data corresponds to a conductivity, a pH, a salt concentration, a light absorption, a florescence, a refractive index, an electrochemical response, or mass spectrographic data;   applying a noise reduction technique to the plurality of signals and the plurality of blocks to generate processed data;   performing a transition analysis on the processed data, to generate transition data, wherein performing the transition analysis includes:
 generating a curve using the processed 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.   
     
     
         24 . The method of  claim 23 , wherein applying a noise reduction technique to the plurality of signals and the plurality of blocks includes selecting a combination of a first block and a first signal from the raw data. 
     
     
         25 . The method of  claim 24 , 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 intervals;   an extent to which one of the plurality of signals saturates the 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; or   a number of inflection points shown by the plurality of signals during a transition phase.   
     
     
         26 . The method of  claim 25 , wherein the profile is associated with a drug product. 
     
     
         27 . The method of  claim 26 , wherein the transition data is indicative of an integrity of a chromatography column used to purify the drug product. 
     
     
         28 . The method of  claim 23 , 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.   
     
     
         29 . The method of  claim 23 , wherein the noise reduction technique includes one or more of:
 analyzing a portion of raw data for dynamic signal errors; or   normalizing a portion of raw data to prevent magnitude bias.   
     
     
         30 . A process control method, comprising:
 receiving raw data from a detector, wherein the raw data corresponds to a conductivity, a pH, a salt concentration, a light absorption, a florescence, a refractive index, an electrochemical response, or mass spectrographic data;   generating processed data by selecting smoothed data matching a feature of a transition;   performing a transition analysis on the processed data to generate transition data, wherein performing the transition analysis includes:
 generating a performance parameter based on the processed 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; 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.   
     
     
         31 . The method of  claim 30 , wherein the feature of the transition includes:
 a derivative duration;   a maximum intensity;   a duration from initiation; or   expected background noise.   
     
     
         32 . The method of  claim 30 , further comprising:
 generating an Individual chart, Moving Range chart, or Range chart.   
     
     
         33 . The method of  claim 32 , further comprising generating performance data by performing a multivariate data analysis to the Individual chart, Moving Range chart, or Range chart. 
     
     
         34 . The method of  claim 33 , wherein the multivariate data analysis includes principal component analysis, partial least squares, orthogonal partial least squares, multivariate regression, canonical correlation, factor analysis, cluster analysis, graphical procedures, or a combination thereof. 
     
     
         35 . The method of  claim 32 , further comprising generating performance data by performing a principal component analysis to the Individual chart, Moving Range chart, or Range chart. 
     
     
         36 . The method of  claim 32 , further comprising:
 generating performance data by performing a principal component analysis or a multivariate data analysis to the Individual chart, Moving Range chart, or Range chart; and   terminating a chromatography process based on the performance data.   
     
     
         37 . The method of  claim 30 , wherein the raw data includes a plurality of blocks and plurality of signals, and the method further comprises selecting a combination of a first block and a first signal from the raw data according to a profile defining a plurality of selection criteria, wherein the profile is associated with a drug product. 
     
     
         38 . A process control method, comprising:
 receiving raw data from a detector, wherein the raw data includes a plurality of signals and plurality of blocks, and wherein the raw data corresponds to a conductivity, a pH, a salt concentration, a light absorption, a florescence, a refractive index, an electrochemical response, or mass spectrographic data;   generating smoothed data by applying a noise reduction technique to the raw data, wherein the noise reduction technique comprises:
 selecting a portion of raw data using predetermined set points; and 
 using a smoothing filter on the portion of raw data to generate smoothed data; 
   performing a transition analysis on the smoothed data 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.   
     
     
         39 . The method of  claim 38 , wherein the noise reduction technique further includes selecting the portion of the raw data using predetermined set points. 
     
     
         40 . The method of  claim 38 , wherein the noise reduction technique further includes:
 analyzing the portion of raw data for dynamic signal errors;   normalizing the portion of raw data to prevent magnitude bias; or   both.   
     
     
         41 . The method of  claim 38 , further comprising:
 generating an Individual chart, Moving Range chart, or Range chart; and   generating performance data by performing a principal component analysis or a multivariate data analysis to the Individual chart, Moving Range chart, or Range chart.   
     
     
         42 . The method of  claim 38 , wherein performing a transition analysis includes:
 generating a performance parameter based on the smoothed 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 in combination with historical data.