Explainable deep learning for improved real-time monitoring of a
chromatographic protein A capture step
Abstract
Model-based real-time monitoring of biopharmaceutical production is a
major step towards Quality-by-Design in this field and the fundament for
model predictive control. Data-driven models have been proven a viable
option to model bioprocesses. In the high stakes setting of
biopharmaceutical manufacturing it is essential to ensure high model
accuracy, robustness and explainability. That is only possible when (i)
the data used for modeling is of high quality, (ii) state-of-the-art
modeling algorithms are employed and (iii) the input-output mapping of
the model has been characterized. In this study we evaluate the accuracy
of multiple data-driven models in predicting the monoclonal antibody
concentration, dsDNA concentration, host cell protein concentration, and
high molecular weight impurity content during elution from a protein A
chromatography capture step. We demonstrate how
permutation/occlusion-based methods can be used to gain understanding on
dependencies learned by of one of the most complex data-driven models;
convolutional neural network ensembles. Finally, we present a workflow
to test the model behavior in case of simulated sensor fouling and
failure. This study represents a major step towards improved viability
of data-driven models in biopharmaceutical manufacturing.