Bizarre paper [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2020-06-08 12:43 (342 d 10:28 ago) – Posting: # 21510
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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


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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