Bioequivalence and Bioavailability Forum

Hi BE-proff,

❝ ❝ Most people are happy with 5×t_½ (96.88% of steady state) whilst others are more strict (7×t_½ 98.44%, 10×t_½ 99.38%

❝ Did you get this information from literature or these figures are your own observations?

We discussed that already, right?

❝ One more question - how would you check if steady state has been reached?

There are some fancy methods (MANOVA, regression of the pre-dose concentrations and testing whether the slope ≠ 0, Hotelling’s T²; see this thread). None of them are really good. Luckily regulators realized that recently and are generally satisfied with:

1. A justification of the dosing regimen in the study (e.g., EMA: saturation ≥5t_½) based on the (average?) half-life reported in the literature.
   • AFAIK, only in Taiwan and China estimation of t_½ in the study is required. Since – especially for MR products – this might be difficult within the dosing interval (flat profile) these poor guys have to sample beyond τ.
2. A table and plots of ≥3 pre-dose concentrations in the saturation phase.

You can also use the quick & dirty method from below: % of steady state = 100×C_pre-dose/C_τ. Please, don’t ask me for a reference!