Data Augmentation to Support Biopharmaceutical Process Development through Digital Models—A Proof of Concept

Abstract

In recent years, monoclonal antibodies (mAbs) are gaining a wide market share as the most impactful bioproducts. The development of mAbs requires extensive experimental campaigns which may last several years and cost billions of dollars. Following the paradigm of Industry 4.0 digitalization, data-driven methodologies are now used to accelerate the development of new biopharmaceutical products. For instance, predictive models can be built to forecast the productivity of the cell lines in the culture in such a way as to anticipate the identification of the cell lines to be progressed in the scale-up exercise. However, the number of experiments that can be performed decreases dramatically as the process scale increases, due to the resources required for each experimental run. This limits the availability of experimental data and, accordingly, the applicability of data-driven methodologies to support the process development. To address this issue in this work we propose the use of digital models to generate in silico data and augment the amount of data available from real (i.e., in vivo) experimental runs, accordingly. In particular, we propose two strategies for in silico data generation to estimate the endpoint product titer in mAbs manufacturing: one based on a first principles model and one on a hybrid semi-parametric model. As a proof of concept, the effect of in silico data generation was investigated on a simulated biopharmaceutical process for the production of mAbs. We obtained very promising results: the digital model effectively supports the identification of high-productive cell lines (i.e., high mAb titer) even when a very low number of real experimental batches (two or three) is available.