Bioequivalence and Bioavailability Forum

Bizarre paper [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2020-06-08 14:43 (1407 d 19:37 ago) – Posting: # 21510
Views: 12,399

Hi Nastia,

THX for the paper! ¹
Regrettably the authors got many things wrong. The FDA does not require AUC_0–t or AUC_0–∞ but both. Reading educates.
The infamous AUCall is nowhere recommended in the Japanese Guideline ² (AUC_t 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.  LLOQ 17% of C_max, fantastic bioanalytics.
This example demonstrates that setting the first value after t_last to zero is nonsense. I have seen splendid rules like “set first one after t_last 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.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• AUCt not covering at least 80% of AUCinf ratnakar1811 2013-03-05 08:30 
  • AUCt not covering at least 80% of AUCinf d_labes 2013-03-05 11:12
    • AUCt not covering at least 80% of AUCinf ratnakar1811 2013-03-06 08:50
      • AUCt not covering at least 80% of AUCinf ElMaestro 2013-03-06 11:10
        • ADME-tox? Helmut 2013-03-06 14:35
          • ADME-tox? ElMaestro 2013-03-06 16:40
            • OT Helmut 2013-03-06 17:19
              • OT ElMaestro 2013-03-07 17:19
                • OT Helmut 2013-03-07 17:26
      • Science vs. regulations Helmut 2013-03-06 14:30
        • Science vs. regulations cakhatri 2013-03-10 08:59
          • ratio = difference of logs! Helmut 2013-03-11 01:17
        • Science vs. (EMA) GL aka PK primer Helmut 2013-03-11 03:17
        • Science vs. regulations qualityassurance 2020-04-23 14:11
          • Science vs. regulations Helmut 2020-04-23 17:32
            • Science vs. regulations Achievwin 2020-05-07 22:59
              • Science vs. regulations Helmut 2020-05-07 23:54
      • AUCt not covering at least 80% of AUCinf Brus 2018-11-20 13:01
        • AUCt not covering at least 80% of AUCinf Astea 2020-06-05 19:05
          • So what? Helmut 2020-06-06 12:02
            • Carrot and whip Astea 2020-06-06 21:11
              • Gedanken­experi­ment Helmut 2020-06-07 12:41
                • Dead dogs mittyri 2020-06-07 20:32
                  • Aber meine Herren das ist keine physik Astea 2020-06-08 00:08
                    • Aber meine Dame, das ist alles Unsinn! Helmut 2020-06-08 01:04
                    • Bizarre paperHelmut 2020-06-08 12:43
                      • Bizarre paper ElMaestro 2020-06-08 15:33
                        • OT: Bias of AUCt, AUCall, pAUC Helmut 2020-06-08 15:53
                          • OT: Bias of AUCt, AUCall, pAUC ElMaestro 2020-06-09 08:45
                            • OT: Bias of AUCs; example Helmut 2020-06-09 14:07
                      • Maxwell's demon Astea 2020-06-12 14:15
                  • Dead dogs Helmut 2020-06-08 10:40