Bioequivalence and Bioavailability Forum

Hi John,

some counter-questions first:

• PPI?
  
• Test or Reference?
  
• Sample size?
  
• 2×2 or replicate?

Since you posted in the Reg/GL-category: I don’t know of any GL specifying what a “reliable profile” is. There was a workshop in Canada a while ago, where TPD claimed two points to be sufficient to calculate AUC and one for C_max (not kiddin’). For EMA you could take the subject out if the AUC is <5% of the rest of the subjects (if prespecified in the protocol). You can perform both evaluations (regulators love sensitivity analyses), but very likely you will fail with the full data set. In the past FDA recommended re-testing of the subject with both test and reference (sample size ≥6 or 20% of subjects, whichever is larger). If the subject show a ‘normal’ profile in the retest you may exclude him/her from the analysis. I’m rather skeptic whether FDA still accepts such a procedure nowadays.