Q. Can one reasonably use estimates from the literature from a population PK analysis of a drug intravenously infused to simulate individual subject plasma data for a BE comparison? Following dialog with the agency, request was to see if a PK simulation can show that a 10% difference in an infusion dose would still be bioequivalent (0.80-12.5) to the original dose? However, the Sponsor has no clinical PK study data with this IV drug (known). Thus looking into literature to obtain parameter and variability estimates. Identified a population PK study of the drug after IV infusion doses which provides NONMEM parameter (RSE%) and intersubject variability (IIV%) (RSE) estimates for each of the CL and Vd’s in the FOCEI with mixed residual error model. Would like to apply these estimates to run simulations with the same pop PK model in Phoenix NLME. What are reasonable variability estimates for this simulation? For example, squaring the reported IIV values (range 0.4 to 0.9) provides an estimate of the omega values for each parameter. Have included in the NLME code for intrasubject variability in the parent CL (13%) for the two period study. What is a reasonable value for the residual error std deviations (0.26 for now) for CEps and MetEps? Looking to simulate plasma data for a hypothetical sample size of 16 subjects for a target infusion dose and another infusion dose that differs by 10%. Initial BE simulation results yielded a GMR of `108.1 and 108.7% for Cmax and AUC but with small 90% CLs (~ 105.8-110.9%).