Bioequivalence and Bioavailability Forum

For BE studies, this guidance recommends measurement of the racemate using an achiral assay. Measurement of individual enantiomers in BE studies is recommended only when all of the following conditions are met:

1. the enantiomers exhibit different pharmacodynamic characteristics,
   
2. the enantiomers exhibit different pharmacokinetic characteristics,
   
3. primary efficacy and safety activity resides with the minor enantiomer, and
   
4. nonlinear absorption is present (as expressed by a change in the enantiomer concentration ratio with change in the input rate of the drug) for at least one of the enantiomers.

In such cases, we recommend that BE factors be applied to the enantiomers separately.

The use of achiral bioanalytical methods is generally acceptable. However, the individual enantiomers should be measured when all the following conditions are met:

1. the enantiomers exhibit different pharmacokinetics
   
2. the enantiomers exhibit pronounced difference in pharmacodynamics
   
3. the exposure (AUC) ratio of enantiomers is modified by a difference in the rate of absorption.

The individual enantiomers should also be measured if the above conditions are fulfilled or are unknown. If one enantiomer is pharmacologically active and the other is inactive or has a low contribution to activity, it is sufficient to demonstrate bioequivalence for the active enantiomer.