Data-driven digital twin models for forecasting multi-step ahead
profiles of mammalian cell culture performance
Abstract
Recently, enormous culture profiles and datasets from biomanufacturing
processes to produce recombinant therapeutic proteins (RTP) such as
monoclonal antibodies (mAbs) could be generated by virtue of the
advancement in process analytical techniques and artificial intelligence
(AI). Thus, now it is highly necessary to develop AI-based data-driven
models (DDMs) and exploit them accordingly in order to further enhance
operational efficiency and accelerate reliable product supply. Since
bioprocess is a complex and dynamic system, DDMs are practical and
particularly useful to describe the intrinsic relationship among
biological and process parameters and cell culture conditions by
capturing inherent patterns and to produce high-quality RTP under
consistent operations as well as to decrease cost and time by predicting
incipient or abrupt faults during the cell cultures. In this work, we
provide the practical guideline for choosing the best DDM on given
mAb-producing Chinese hamster ovary (CHO) cell culture data sets,
enabling us to forecast culture performance such as VCD, and mAb titer
as well as glucose, lactate and ammonia concentrations in real time
manner. Via the case study with 32 fed-batch data sets of CHO cell
cultures, we suggested best combination of model elements including AI
algorithms and multi-step ahead forecasting strategies, for good
prediction in terms of the computational load as well as the model
accuracy and reliability, which is applicable to implementation of
interactive data-driven model within bioprocess digital twins. We
believe this systematic study can help bioprocess engineers to start
developing predictive DDMs with their own data and learn how their cell
cultures behave in near future, thereby making proactive decision
possible.