Exploring the potential of machine learning for more efficient development and production of biopharmaceuticals.

Principles of Industry 4.0 direct us to predict how pharmaceutical operations and regulations may exist with automation, digitization, artificial intelligence (AI), and real time data acquisition. Machine learning (ML), a sub-discipline of AI, involves the use of statistical tools to extract the desired information either through understanding the underlying patterns in the information or by development of mathematical relationships among the critical process parameters (CPPs) and critical quality attributes (CQAs) of biopharmaceuticals. ML is still in its infancy for directly supporting the quality-by-design based development and manufacturing of biopharmaceuticals. However, adoption of ML-based models in place of conventional multi-variate-data-analysis (MVDA) is increasing with the accumulation of large-scale data. This has been majorly contributed by the real-time monitoring of process variables and quality attributes of products through the implementation of process analytical technology in biopharmaceutical manufacturing. All aspects of healthcare, from drug design to product distribution, are complex and multidimensional. Thus, ML-based approaches are being applied to achieve sophistication, accuracy, flexibility and agility in all these areas. This review discusses the potential of ML for addressing the complex issues in diverse areas of biopharmaceutical development, such as biopharmaceuticals design and assessment of early stage development, upstream and downstream process development, analysis, characterization and prediction of post-translational modifications (PTMs), formulation, and stability studies. Moreover, the challenges in acquisition, cleaning and structuring the bioprocess data, which is one of the major hurdles in implementation of ML in biopharma industry, have also been discussed. Regulatory perspectives on implementation of AI/ML in the biopharma sector have also been briefly discussed. This article is a bird's eye view on the recent developments and applications of ML in overcoming the challenges for adopting "Industry - 4.0" in the biopharma industry.