When a pharmaceutical process was transferred from lab to industry, the process scale became a new variable which had impacts on the product quality. Under the framework of pharmaceutical quality by design (QbD), the addition of process scale as a new variable need further understandings of pharmaceutical processes. This paper summarized common methods for pharmaceutical scale-up study. In particular, mathematical modeling and simulation based scale-up methods were introduced in detail. The high shear wet granulation process was selected as an example. Dimensionless analysis was performed to maintain the similar dynamics and thermodynamics of micro environment of particle growth at different scales. And then process dynamic design space was built and was dimension independent. The boundary and range of process design space were extended. The tolerance of process for changeable variables was improved and quality variability of the product was well controlled.