DIGITAL TWINS FOR CMC SIMULATING PROCESS VARIABILITY TO INFORM PROGRAM DECISIONS

The Digital Twin technology is currently becoming an innovative instrument in Chemistry, Manufacturing, andControls (CMC), allowing to simulate specific variability of the process precisely and make essential programdecisions based on these simulations. This paper shows that digital twins are useful in predicting interactionsbetween Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) throughout pharmaceuticalproduction. Enabling real-time performance of processes under different conditions, digital twins can be used tosimulate processes and, thus, guide sound decision-making by creating a virtual replica of manufacturingprocesses. The method increases the understanding of processes because it measures how variability influencesproduct quality to determine the best control measures. In addition, digital twins help in making informeddecisions in make-or-buy analyses, by modeling in-house manufacturing and outsourcing situations. They are alsoable to offer critical insights on site-readiness assessments, where it can be determined in advance whethermanufacturing sites can deliver process requirements before actual deployment. Computer simulations and highquality models are used to combine experimental data with sophisticated modeling methods to improve predictivequality of digital twins, including mechanistic models and data-driven models. Case studies describe effectiveuses in the case of continuous biologics production and the purification of monoclonal antibodies, where digitaltwins can reduce the time to development, without compromising regulatory standards. Finally, the methodologyunderpins Quality by Design (QbD) and Process Analytical Technology (PAT) approaches by giving a dataoriented basis of risk-based decisions. Simulations on digital twin decrease uncertainty, build efficiency, andfacilitate sustainable production practices within the pharmaceutical industry. The findings emphasize theimportance of digital twins to streamline CMC strategies, enhance the quality of products assurance.