Bioequivalence and Bioavailability Forum

Dear all,

two participants of the recent survey commented that the “Bracketing Approach” (e.g., non-superiority of C_max, non-inferiority of C_min)* and testing for equivalence of AUC is not available in the software they are using most (without naming it).

In PowerTOST it is implemented (see its vignette for examples). Since the CV of AUC is generally lower than the ones of C_max/C_min it will not drive the sample size.

---

• EMA, CHMP. Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms. London; 20 November 2014. EMA/CHMP/EWP/280/96 Rev1.
  “5.1.1. Waiving of therapeutic studies
  C_max,ss for the new MR formulation is below or equivalent to the C_max,ss for the approved formulation and C_min,ss for the MR formulation is above or equivalent to the C_min,ss of the approved formulation.”