The Population Simulator Mode and Virtual Bioequivalence
Population Simulator is one of the simulation modes that is available in GastroPlus®. In this mode, you can run simulated clinical trials for virtual subjects, combining physiology and pharmacokinetic variability within populations and considering formulation variables that were used as input data in the software.
As per the FDA, bioequivalence (BE) is the absence of a significant difference in the rate and extent that an active ingredient in pharmaceutical equivalents has contact with the site of the drug's action. To demonstrate BE, trials must be conducted in which a test product must duplicate the Cmax and AUC of a reference product within 80-125% at 90% confidence intervals under both fasted and fed conditions for trial subjects. Implicit in this approach, however, is that the number of subjects in the BE trial can affect the outcome of the trial. If the number of subjects is too small, then the trial might fail. Conversely, if the number of subjects is too large, then time and money are wasted.
This section details the use of population simulations in the Virtual Bioequivalence (VBE) run mode to conduct VBE trials, where VBE is defined as the demonstration of BE using modeling and simulation in lieu of clinical studies. In a VBE trial, you can run a series of simulations with different simulated subjects, each of which is described by a sample of physiological and pharmacokinetic parameters to imitate a population, and formulation variables to imitate the variances expected with actual formulations. You can then assess the combined effects of variations in population physiology and confirm the consistency in the trend between the Cmax and AUC ratios to assist in determining BE.
This section covers the following topics: