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IVIVR establishment and BE predictions 

In Silico trial to establish a IVIVR model based on Bioequivalence outcome


The Sponsor intended to have a bio-predictive media followed by IVIVR model to predict the plasma exposure for different in-vitro release and different doses. The Sponsor had performed a BA BE study on the higher strength.

Question of Interest

Could Modeling and Simulation predicts the BE outcome without conducting actual BA BE study? 


BA BE data of the test product and the reference were used in the analysis.

The in silico BE predictions were done by means of IVIVC modeling followed by virtual BE


A validated IVIVC model (see figure) was developed and used to simulate the “BE outcome”.  

  Based on the established and validated IVIVR model (in water) for Carbamazepine ER tablets 400 mg of reference and test product, test product of Carbamazepine ER tablets 100 mg (lower strength) is exhibiting bioequivalence (T/R is 1.03 & 1.04 for Cmax & AUC respectively) with the Reference product Tegretol XR Tablets 100 mg.
Model building Drug Record Cmax (µg/mL) AUC (µg/mL*h)
Obs. Pred. % Pred. Error Obs. Pred. % Pred. Error
IVIVR model established CBZ Pivotal Test 400 mg (E21122977) Water 3312.3 3316.7 0.133 2.43E+05 2.32E+05 4.262
IVIVR model validation CBZ Pilot Test 400 mg Water 3345.1 3242.9 3.055 1.84E+05 1.71E+05 7.094
IVIVR model – External predictability CBZ Ref 400 mg (FX000895) Water 3211.2 3175.1 1.125 2.37E+05 2.17E+05 8.642


The M&S methodology for IVIVR model building predicted the BE outcome for different in-vitro release profile.

The Sponsor reduced costs and timelines by decreasing the development timeline and number of clinical studies

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