Scaling for pAUCs [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2013-03-15 15:19 (4030 d 20:29 ago) – Posting: # 10201
Views: 23,148

Dear all!

Lines 800/805:
AUC(0-t) and AUC(0-∞). No truncation (line 788). I’m happy with that. Avoids problems with potential flip-flop PK of CR formulations (EMA’s terminology: prolonged release). I would say if we show BE of AUC(0-∞), BE of AUC(0-t) is of no additional value.1 Furthermore, in a linear system only SD AUC(0-∞) is expected to be equal to MD AUC(0-τ). On the other hand, IMHO for DR AUCt or AUC72 should be sufficient.
No BE of “partial Cmax” like in the Q&A-document Section 11.2 Should be determined (lines 789/790) but not compared (i.e., not stated in lines 800–804). This is now in line with FDA’s requirements.

Lines 807–810:
Scaling is acceptable for HVD/HVDPs – not only for Cmax,ss, but also for Cτ,ss and pAUC. Though I expected Cτ,ss – pAUC is a positive surprise. For the latter I know of one product already passing last year after a scientific advice at EMA (terrible CVWR of the first pAUC was demonstrated in full replicate pilot study).


  1. AUC(0-∞) and AUC(0-t) are highly correlated. Since the variability of the former is higher than the one of the latter if a study passes AUC(0-∞) likely it will pass AUC(0-t) as well. Hint: Intersection-Union Tests.
  2. The last paragraph reads:
    “These recommendations are based on the present Note for guidance on modified release oral and transdermal dosage forms, Section II (CPMP/EWP/280/96) and represent the current regulatory thinking. It should be noted that this guideline is currently under revision hence recommendations regarding these aspects may change in the revised guideline.”

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,639 registered users;
82 visitors (1 registered, 81 guests [including 4 identified bots]).
Forum time: 11:49 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5