This work details development of a system/process model and usage of Computer Experiments methodology for continuous manufacturing of Active Pharmaceutical Ingredients (API). The process of interest has three interconnected continuous unit operations, with the first two being reactors and the last being an evaporator. The overall workflow detailed can be summarized as follows: a) develop mechanistic process models, b) verify/validate the model, c) convert model parameters to process parameters d) design computational grid to simulate the model-Latin hypercube design in this case, e) perform simulations, f) fit meta-model (surrogate model) to the output parameter/attribute of interest, g) analyze the meta-model using global sensitivity analysis, and h) slice and dice the model, e.g., study response surfaces of interest, for further analysis. This workflow has several practical advantages in process development, optimization, and troubleshooting, especially when the number of process inputs and/or parameters are large and/or output response surfaces are potentially complex. Phenomenological model development is detailed for biphasic reaction with large solvent volume change. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.