Bioequivalence and Bioavailability Forum

❝ What is Dose Normalization?

❝ If possible please provide the links for reading.

1. In the first step of assessing dose-proportionality, dose-linearity is checked by conventional BE. For instance you have three formulations with 10/20/40mg, where you have already shown BE to the reference product with 20mg. You may run a 3-way study of your test formulations (10/20/40mg) and set the 20mg as the reference. Now you dose-normalise the 10mg and 40mg results (AUC, C_max) to 20mg (10×2, 40/2) and perform a conventional BE comparison to the 20mg formulation.
   S-C Chow and J-p Liu
   Design and Analysis of Bioavailability and Bioequivalence Studies
   Marcel Dekker, New York (3^rd ed. 2008)
   I would recommend to use a Bonferroni-correction (i.e., use a 95% confidence interval insted of a 90% in order to keep the overall risk ≤5%).
   
2. In Canada you have to present BE based both on the declared content (i.e., assuming D_test = D_reference) and corrected for actual content. This method is unique and most likely will be removed in the next revision. WHO recommended this method in 1995, but removed it in 2006. In the US and the EU a correction for actual content is generally not acceptable.