Bioequivalence and Bioavailability Forum

Dear All,

Please give your valuable inputs.

We have performed 2x2 fasting BE pivotal study for USFDA after seeing pilot study results.

We've noted following from pivotal study data,

• 90% CI for C_max and AUC_0-t was within 80.00-125.00% and for AUC_0-inf upper limit was not within the BE limit, this is due to one subject (T/R was >3000%; T½ is >1000 hrs; AUC extrapolation was 99% for this subject). After reaching T_max at 2.00 hr the concentration declined and reached BQL in 12 hours and after that few measurable concentrations was observed in 14 hr, 16 hr & 18 hr in elimination phase.
  
• Similar case was NOT observed in the pilot study.

How to handle this subject’s data? Outlier? Can the regulatory accept the based on C_max and AUC_0-t results?

Can we select the time point manually for K_el calculation instead of best fit method by the tool?

Thanks & Regards
NK

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Edit: Category changed; see also this post #1. [Helmut]