This article describes the process characterization and development of models to inform a process control strategy to prepare (R,R)-epoxy ketone 2, an intermediate in the manufacture of carfilzomib. Model calibration for relevant unit operations and the development of a dynamic integrated flowsheet-level model in gPROMS FormulatedProducts software enabled investigation of the impact of process disturbances and model uncertainties on the critical quality attributes (CQAs) and identification of critical process disturbances and failure modes to guide a process control strategy. The model development was similar to that described in the previous parts of this series, but with the added complexity of comparing two distinct kinetic formulations for the epoxidation reaction. The main CQAs for this process were (1) the conversion of enone 1 (target ≥99.0 mol % conversion) and (2) the purity target for solids prior to cake wash (target ≥97.5% purity by weight). Conversion of enone was not always achieved with the expected disturbances: whereas 99.5% conversion was expected for normal operating conditions, 97.2% conversion was predicted for the worst-case combination of disturbances. The chiral purity of crystalline (R,R)-epoxy ketone 2 was not always achieved with the expected disturbances: 98.2% purity was expected for normal operating conditions, and 96.7% purity was expected for the worst-case combination of disturbances. These analyses allowed for rank ordering of critical process parameters that impact conversion and suitable manipulated variables to develop a robust process control strategy for the manufacturing scheme.