Bioequivalence and Bioavailability Forum • Science vs. regulations

Science vs. regulations [Regulatives / Guidelines]

posted by Achievwin – US, 2020-05-08 00:59 (1674 d 12:43 ago) – Posting: # 21404
Views: 19,329

Good discussions:

❝ ❝ For reference: Tmax: 0.67, Tlast: 28.25

❝ ❝ For test: Tmax: 0.50, Tlast: 23.91

Aren't we lost in pure numbers and forgot to look at the individual curves?
In order to have accurate AUC estimations you need to have at least two measurable concentrations (non-BQL) before Tmax and as many time points as possible on either side of Tmax.

With 067 and 0.50 hours as Tmax how many blood draws you can practically take (assuming this is an oral formulation) may be we have to go to IV blood sampling schedule.

I saw somewhere blood samples were taken 24 and 48 hrs (assuming these are ambulatory samples there will be lot of time variation.), Hardly we completed 1 or 2 half lives. and we expect to cover 80% AUC?

Even assuming we covered AUC there is always some bad apples, in my experience due to some bad data points in the extremes you may tend to have all kinds of elimination patterns (positive slope, bad two many missed blood draws or BQL values… so it is not surprising that AUC% is less than 80% in more than 30% subjects what is that 30% in 12 or 18 subjects?

If i am designing study I take following precautions (everyone knowns these things but I am listing)

see you heavy sampling either side of your Tmax (this covers majority of the AUC and accurately determines Cmax).
Ensure you have at least two blood draws for every half life
Capture blood draws up to 4 half lives, if your assay permits your half life is not long

Then a priori in the protocol SAP include limitations on reporting AUCinf and %Extrp.

R2>0.800
AUC% Extrp should be more than 80%
if two consecutive blood draws are BQL and hen you see a reportable value in elimination phase no kEL, t1/2 aucINF % etrp will not be reported , at least FDA understands that AUCinf some times is skewed and excluding some subjects is always allowed with proper explanation.

Hope this helps.

Edit: Please don’t shout! [Helmut]

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. regulations Helmut 2020-04-23 17:32
        
        Science vs. regulationsAchievwin 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