Application of advanced machine learning algorithms for anomaly detection and quantitative prediction in protein A chromatography

ElsevierVolume 1682, 25 October 2022, 463486Journal of Chromatography AHighlights•

Advanced ML algorithms for column integrity breach and yield prediction have been proposed.

PCA followed by IF and LSTM AE were utilized to detect column integrity breach.

Both algorithms successfully predicted the column integrity failure 4 cycles in advance.

PLS-ANN model was utilized for yield prediction and compared with PLS and ANN.

PLS-ANN model outperforms with R2 and RMSE values of 0.96 and 0.014 respectively.

Abstract

Protein A capture chromatography, which forms the core of the mAb purification platform, demands cautious use and maximum resin utilization due to high cost associated with resin. In this paper, we propose an application of advanced machine learning (ML) algorithms to address two most crucial objectives of column integrity breach and yield prediction for resin cycling study of protein A chromatography. Two approaches have been considered to detect anomalies in case of column integrity breach. The first approach utilized the traditional Principal Component Analysis (PCA) method for dimensionality reduction followed by anomaly detection using Isolation Forest (IF) algorithm. The second approach involved the application of deep learning neural network based Long Short Term Memory autoencoder (LSTM AE). Both the algorithms could successfully predict the column integrity failure 4 cycles ahead of the actual cycle. In the case of prediction of percentage yield decay, a partial least squares-artificial neural network (PLS-ANN) augmented model was utilized and compared with the traditional PLS regression model. The developed PLS-ANN model with higher R2 and lower RMSE values of 0.96 and 0.014 respectively could outperform the classical PLS model with lower R2 and RMSE values of 0.88 and 0.028, resulting in more accurate yield prediction. The developed ML algorithms for both case studies could not only successfully forecast anomalies by detecting subtle changes in column packing quality and thereby facilitate real time control decisions for preventive measures, a prerequisite for continuous manufacturing, but also demonstrated the ability to predict complex yield decay behaviour for protein A chromatography. As biopharmaceutical manufacturing adopts continuous processing, copious amount of data will be generated from the process and analytical equipment on the manufacturing floor, and the proposed advanced ML algorithms have significant potential in dealing with nonlinearities of the different unit operations simultaneously and facilitate real-time control decision making.

Keywords

Protein A chromatography

Resin cycling

Machine learning (ML)

Continuous processing

Data Availability

Data will be made available on request.

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