Abstract
Pharma 4.0 has continued to advance as the industry develops advances in process analytical technologies, automation, and digit-ization. Digital twins which transform on-line process measure-ments into meaningful outputs in real-time are being developed to seize the opportunity made possible with this shift. Digital twins can be used for improved process optimization on a range of scales, from determining optimal metabolite concentrations in upstream bioreactors to considering economic and environmental impacts of process decisions. In this paper, we explore the current uses of digital twins in solid-based pharmaceutical space and the bio-pharmaceutical manufacturing. Applications cover scale up of upstream processes, product quality control, and consideration of continuous systems. We also describe the intersection of digital twins in flow sheet modeling, sensitivity analysis and optimization, and design space evaluation. Finally, areas requiring further im-provement for industry adoption are addressed.