A digital twin of lyophilization units was developed to facilitate the scale-up of the lyophilization process from the laboratory to the commercial scale. Our focus was on ensuring successful technology transfer for manufacture of high-quality drug products. Traditionally, lyophilization models have been specific either to the equipment or to the vial. In this study, we integrated the equipment and the vial models in a way that they mutually influenced each other via boundary conditions (two-way coupling). We conducted two sets of calculations. Firstly, we performed steady-state simulations using Computational Fluid Dynamics (CFD) to simulate an ice slab test, which helped determine the equipment capability curve. Secondly, we carried out transient, coupled simulations using a coupled 3-D CFD and 1-D vial scale simulation model to mimic the primary drying phase in a lyophilizer. Using the coupled 3-D CFD and 1-D vial scale model, we were able to determine the product temperature, the sublimation rate and the cycle time based on the temporal and spatial conditions in the lyophilizer. The coupled approach was then applied to capture the effects of process disturbances and failure conditions in the lyophilizer, which enables a more robust process design.