Bioequivalence and Bioavailability Forum

❝ Kindly give your suggestion about how the agency will take this issue and is it affect the study?

Any agency may question reliability of Cmax assessment in such case. And they often do.
The only way to see whether this affects the study, is to recalculate study results with all subjects with Cmax at first time point excluded. If your recalculated results remains within acceptance criteria then you can state that Cmaxes at first time point had no impact on study conclusions.
If however these results don't show bioequivalence, there is great risk of study rejection. Especially if there was possibility of including additional, early blood samples. And there was as you're saying about first sample at 0.5h. Literature data of Cmax starting with 1 hour will rather not help you. Your sampling scheme was not adequate for proper Cmax characterization in this study - whether it was justifed at the time of study planing or was not, is secondary in this case.
This is what I can say from my experience with EU agencies.
Best regards,
Lukas