Bioequivalence and Bioavailability Forum

Hi Relaxation,

❝ ❝ 5. \(\small{_\textrm{partial}AUC_{\textrm{cut off}-{\tau}}}\)

❝

❝ This one I think should be: \(\small{_\textrm{partial}AUC_{\textrm{cut off}-t_\textrm{last}}}\)?

According to the GL, yes. However, doesn’t make sense to me.¹ In trying to get a waiver for the MD study I’m interested in showing BE for the partial \(\small{AUC\textrm{s}}\), which are – hopefully – predictive of the clinical situation (multiple doses administered with \(\small{\tau}\)). If you have issues with the LLOQ in the SD study or missing sample(s) in the late part of the profile, already \(\small{AUC_{0-t_\textrm{last}}}\) [sic] is a pile of poo.

If in a subject \(t_\textrm{last(T)}\neq t_\textrm{last(R)}\), that’s comparing apples with oranges (though similar by weight and shape, extremely different by smell, taste, touch, and texture).
IMHO, it’s high time to abandon \(\small{AUC_{0-t_\textrm{last}}}\) in all guidelines (because biased) and move forward to the – always (‼) unbiased – \(\small{AUC_{0-t_\textrm{last(Common)}}}\).²

Confession: In my studies of multiphasic products I chickened out and used still \(\small{AUC_{0-t_\textrm{last}}}\) (I knew that I won’t have problems with BQLs and wanted to make assessors happy) but \(\small{_\textrm{partial}AUC_{\textrm{cut off}-{\tau}}}\). Were accepted without problems.

---

1. Remember Henning’s credo of ‘Science-based Regulations’!
   
2. Fisher D, Kramer W, Burmeister Getz E. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: t_last (Common). J Clin Pharm. 2016; 56(7): 794–800. doi:10.1002/jcph.663. free resource.