In the pharmaceutical and specialty chemical industries, faster time-to-process is a significant measure of success. In these industries, modular plants made up of Process Equipment Assemblies (PEA) are of significant interest due to high flexibility and good scalability. These PEAs are designed according to VDI 2776 [1] and automated according to VDI/VDE/NAMUR 2658 [2]. However, a specific challenge stems from assuring sufficient product quality required by different regulating bodies such as the FDA. Here, the application of Quality by Design methodology, which focuses on a more detailed understanding of the process and enables targeted influencing of product quality, could be advantageous [3]. The central element in Quality by Design is the so-called design space (DS), which describes the behavior of the process in the plant in a defined area and could also be captured with simulation models. To this end, the PEA manufacturer could integrate valuable prior knowledge to support a framework for model-based design of experiments, parameter estimation, and design space identification into a Digital Twin of PEA [4]. The aim of the presentation is to demonstrate how the Quality by Design methodology can be integrated into Digital Twin concept for scale-up in modular plants. To illustrate this concept, a prototypical implementation using the process simulation tool gPROMS is presented for the specific use case of scale-up of an esterification process in a stirred tank reactor type PEA.