This work investigates the behavior during freeze-drying of packing structures formed by spray-frozen microparticles. A multi-scale approach is used to study spray freeze-drying, and in particular, mass transfer during primary drying and its duration. The procedure starts with the generation of realistic packings of microparticles using DEM, and CFD simulations are used to determine some relevant characteristics at pore scale, i.e., porosity, tortuosity, the average size of the particle-to-particle voids, and permeability. Finally, these parameters are used to describe mass transfer within the packed-bed. This procedure is used to describe some actual case studies and evaluate drying time and mass transfer resistance within the packing. We also investigated the role of packing structure on freeze-drying by generating packings from monodisperse and Gaussian-polydisperse microparticles, demonstrating that polydispersity increased the mass transfer resistance, and, finally, drying time.