This paper presented how to establish a clinically relevant specification (CRS) using in silico physiologically based pharmacokinetic (PBPK) modeling. Three different formulations of model drug products were used in the clinical studies in order to distinguish between bioequivalent (BE) batches from non-BE batches. A human PBPK model was constructed by integrating the clinical and non-clinical observations by using GastroPlusTM software. The developed model was verified by the comparison between human PK behavior observed in clinical studies and human PK behavior predicted from the software. The simulation results were obtained by using the dissolution profiles showing clinically relevant discriminatory power as input variables for the developed PBPK model. For three investigated formulations, the simulated PK behavior was comparable to the PK behavior observed in clinical studies. In addition, in silico BE simulation studies confirmed that the verified PBPK model can successfully reproduce the clinical study results. In conclusion, a CRS was established with the BE simulation by using the verified PBPK model, in order to detect and reject non-BE batches of drug products. The establishment of the CRS is useful for a quality control and finding optimal formulation to accomplish target PK behavior, safety, and efficacy.