A new model of whey protein thermal inactivation has been combined with a CFD model developed for skim milk spray drying. Extensive evaporation and particle formation models were used to calculate particle moisture contents, temperatures and residence times. Calculated parameters were then used as input data for an experimentally developed quality model based on Williams-Landel-Ferry (WLF) equations for inactivation kinetics. The developed quality model was implemented into the CFD code and calculated in parallel to simulations of skim milk droplets evaporation based on the characteristic drying curve approach. The quality model and the simulation procedure were validated by comparison of protein activity levels obtained from the CFD with data obtained from differential scanning calorimetry (DSC) of milk powder samples collected during skim milk spray drying experiments. The simulations for different feed rates fit well with measurement results and show that the loss of whey protein activity is lower at higher feed rates, due to lower temperature fields in this case. (C) 2017 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.