Bioequivalence and Bioavailability Forum • Science vs. regulations

Science vs. regulations [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2020-04-23 19:32 (1629 d 12:55 ago) – Posting: # 21347
Views: 18,101

Hi qualityassurance,

that’s an interesting case.

❝ ❝ • Observed t_½ (x±SD, range)?

❝ For reference (10.03 ±4.09, 3.5-19.0)

❝ For test (9.2 ±2.96, 3.22-17.0)

❝

❝ ❝ • t_max, t_last?

❝ For reference: Tmax: 0.67, Tlast: 28.25

❝ For test: Tmax: 0.50, Tlast: 23.91

I played around with your data. Such an early t_max means that this IR product acts practically like a solution (absorption t_½ 10–15 minutes). However, there is an extreme between-subject variability in elimination. That’s why you missed the 80% rule in some subjects.
In retrospect it would have been better to opt for truncated AUC_0–72. Then you would not have to worry about extrapolation.
However, think about the subject line of the post. At 2×t_max absorption is practically complete (~96.12%). You could even take a very conservative approach with 4×t_max (~99.85%). We are interested in comparing the performance of the formulations, not to assess its well-known PK, right?
Hence, scientifically the large extrapolated AUC you see in some subjects is not relevant at all. Kamal Midha showed this nice example of partial AUCs. Once absorption is essentially complete, later T/R-ratios are extremely stable – only their variability increases.
If the assessor prefers to “tick-the-box-in-the-form”, cards are stacked against you. Sorry.

❝ Forgive me for the formatting. I tried my best.

No worries; I edited your post a bit.

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Helmut Schütz

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Science Quotes

Complete thread:

AUCt not covering at least 80% of AUCinf ratnakar1811 2013-03-05 08:30 [Regulatives / Guidelines]
- 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. regulationsHelmut 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 paper Helmut 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