Bioequivalence and Bioavailability Forum

Hello All,

Please provide your input for the following,

As per the FDA guideline

If the pre-dose concentration is ≤ 5 percent of the Cmax value in a subject with a pre-dose plasma concentration, applicants can include the subject’s data without any adjustments in all PK measurements and calculations. We recommend that if the pre-dose value is > 5 percent of the Cmax, applicants drop the subject from all BE study evaluations.

My question here is,

In a BE study of FDC (or drug with two isomers), If any subject had pre-dose > 5 percent of the Cmax for one drug (or one isomer), What should be followed

1. Drop the subject from the statistical analysis of both the drug (or both the isomer) or
   
2. Drop only for the statistical analysis of a drug (or a isomer) for which the pre-dose observed was > 5 percent of the Cmax and include for other drug (or isomer).

Regards
NK