Bizarre paper [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2020-06-08 12:43 (421 d 05:31 ago) – Posting: # 21510
Views: 7,188

Hi Nastia,

THX for the paper! 1
Regrettably the authors got many things wrong. The FDA does not require AUC0–t or AUC0–∞ but both. Reading educates.
The infamous AUCall is nowhere recommended in the Japanese Guideline 2 (AUCt as everywhere else). Given, the “80% rule” is mentioned as well. The Q&A 3 is more specific and states in A-28:

AUC is calculated by a trapezoidal rule as the area under the straight lines connecting the measured points.

(my emphasis)
OK, the bloody linear trapezoidal but can we measure zero? Nope.

Hence, this one

[image]


as the base of all simulations is already wrong and IMHO, the article missed the point.
BTW, this figure is extremely funny cause AUCall is >100% of AUCinf. Rule fulfilled → tick the box → mission accomplished. :crying: LLOQ 17% of Cmax, fantastic bioanalytics.
This example demonstrates that setting the first value after tlast to zero is nonsense. I have seen splendid rules like “set first one after tlast to LLOQ/2 and keep subsequent ones as BQL”. Here also >100% of AUCinf. Forget it.


  1. Oishi M, Chiba K, Fukushima T, Tomono Y, Suwa T. Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment. Drug Metab Pharmacokinet. 2012;27(6):658‐662. doi:10.2133/dmpk.DMPK-12-RG-033.
  2. PMDA. Guideline for Bioequivalence Studies of Generic Products. Feb 29, 2012.
  3. PMDA. Q&A. Feb 29, 2012.

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Helmut Schütz
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