In a traditional assessment of bioequivalence of two formulations of a drug, one compares the average bioavailability form the two formulations. In early 1990s, statisticians and clinical pharmacologists pointed out in some situations, it is not sufficient to demonstrate average bioequivalence, and they proposed to compare the individual responses to the two drug formulations within the subjects. This method is called individual bioequivalence (IBE). At the same time, population bioequivalence (PBE) was also proposed to compare the marginal or population distributions of bioavailabilities. The new approaches overcome the main weakness the main weakness of ABE by considering the variability of the bioavailabilities in addition to their means. PBE, which is defined as ?(µ_T-µ_R)?^2+(s_T^2-s_R^2) which is the difference of the square of between test and reference difference ?(µ_T-µ_R)?^2+(s_T^2+s_R^2) and the square of reference to reference difference 2s_R^2. It is compared to ?_BE·max?(s_0^2,s_R^2) for equivalence, where ?_BE=(?(ln?(1.25)?^2+?_P))/(s_0^2 ), s_0=0.2 and ?_P=0.02. In another word, PBE is determined by a function of ABE margin. PBE approach was further recommended to serve as the approach for in-vitro and CMC equivalence. In this presentation, we discuss the weakness of using PBE to assess in-vitro, CMC and analytical equivalence.