Palladium membrane technology has shown promising features for the development of a sustainable hydrogen economy. Nonetheless, the contribution of a palladium membrane technology to economic and societal development requires its commercialization, diffusion and utilization. To generate enough incentives for commercialization, it is necessary to demonstrate the scalability and robustness of the membranes in industrial settings. Consequently, this work utilizes pilot-scale experimental data generated under industrial conditions to validate a Computational Fluid Dynamics (CFD) model, which was up-scaled and utilized to determine the intrinsic phenomena of palladium membrane scale up. This study reveals the technical/engineering requirements for the effective design of large scale multitube membrane modules. Mass transfer limitations and concentration polarization effects were studied quantitatively with the developed model using the defined parameters Concentration Polarization Coefficient (CPC) and Effective Average CPC (EAC). Methods for diminishing the concentration polarization effect were proposed and tested through the simulations such as i) increasing convective forces and ii) designing baffles to create gas recirculation. For scaled-up membrane modules, mass transfer limitation is an important parameter to consider as large modules showed severe concentration polarization effects. Certainly, this work shows for the first time the main features required when designing large scale membrane reactor modules.