Demonstration of equivalence in aerodynamic particle size distribution (APSD) is one key component for establishing bioequivalence of orally inhaled drug products. We previously proposed a modified version of the Chi-square ratio statistic (mCSRS) for APSD equivalence testing and demonstrated that the median of the distribution of the mCSRS (MmCSRS) is a robust metric when test (T) and reference (R) cascade impactor (CI) profiles are identical. Here, we systematically evaluate the behavior of the MmCSRS when T and R CI profiles differ from each other in their mean deposition and variability on a single and multiple sites. All CI profiles were generated by Monte-Carlo simulations based upon modified actual CI data. Twenty thousand sets of 30 T and 30 R CI profiles were simulated for each scenario, and the behavior of the MmCSRS was correlated to metrics that characterize the difference between T and R product in mean deposition and variability. The two key findings were, first, that the MmCSRS is more sensitive to difference between T and R CI profiles on high deposition sites, and second, that a cut-off value for APSD equivalence testing based on the MmCSRS needs to be scaled on the variability of the R product. The former is considered as beneficial for equivalence testing of CI profiles as it decreases the likelihood of failing identical CI profiles by chance, in part, due to increasing analytical variability associated with lower deposition sites. The latter is expected to be important for consistently being able to discriminate equivalent from inequivalent CI profiles.