Bioequivalence and Bioavailability Forum

Hi Dr Dan and ElMaestro,

Like I said I wasn't really thinking when I wrote that post. Anyhow here is the issue:

1. Partial 3-way replicate pilot study with n=55, ISSD (intrasubject SD) of Ref ~ 0.5-0.55, T/R ratio was 95% (Cmax); AUC T/R Ratios ~ 92%; 95% upper bound limit were less than 0, (like -0.06 to -0.1)
   
2. Partial 3-way replicate pivotal study with n=60, ISSD of Ref ~ 0.55, T/R T/R Ratio for Cmax ~ 82%; AUC Ratios ~ 78%! All 95% UCL were less than 0 (~-0.04-0.06).

Both studies used the same lot of reference. Test product was scaled up to pivotal from pilot with no changes (assured by my friends, same site, same equipment, same batch size yada yada).

I looked at study #2 in terms of Reference arm 1 and Reference 2. Did a comparison between the two (R1/R2), the AUC ratios were 0.85% (Cmax ~ 91%). I did the same thing for study #1. R1/R2 ratios for AUC and Cmax were 98% and 96%.

I guess it's just the nature of the HVD but I am kind of surprise by how different the Reference behaved that's all.

Would sample size help in this regard or even with an increase in sample size the outcome is still trivial?

John