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RegisterScaling for pAUCs [Regulatives / Guidelines]
posted by Helmut 
– Vienna, Austria, 2013-03-15 15:19 (4432 d 08:17 ago) – Posting: # 10201
Views: 26,631
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).
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).
- 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.
- 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.”
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
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:
- Draft EMA MR formulations GL published! Ohlbe 2013-03-15 12:10 [Regulatives / Guidelines]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Housekeeping suggestions Helmut 2013-03-15 13:28
- Scaling for pAUCsHelmut 2013-03-15 14:19
- Draft EMA MR formulations GL published! ioanam 2013-03-30 17:54
- Topicals → 1995 NfG Helmut 2013-03-30 22:51
- Topicals, generic ElMaestro 2013-03-31 19:26
- Topicals, generic ioanam 2013-04-01 07:51
- Topicals, generic The Outlaw Torn 2013-04-01 08:03
- Topicals, generic ioanam 2013-04-01 07:51
- Clarity on waiving multiple dose study Tina 2013-05-15 14:19
- Hey, it is just a draft! Helmut 2013-05-17 18:49
- Critical review of García-Arieta et al. (2012) Helmut 2013-06-29 19:44
- Hey, it is just a draft! Helmut 2013-05-17 18:49
- SD vs. MD, partial AUCs Helmut 2013-06-21 19:24
- SD vs. MD, partial AUCs Shuanghe 2013-06-25 17:22
- SD vs. MD, partial AUCs Helmut 2013-06-25 19:15
- SD vs. MD, partial AUCs Shuanghe 2013-06-27 11:07
- pAUCs, alternative metrics, alcohol Helmut 2013-06-27 14:38
- SD vs. MD, partial AUCs Shuanghe 2013-06-27 11:07
- SD vs. MD, partial AUCs Helmut 2013-06-25 19:15
- SD vs. MD, partial AUCs Shuanghe 2013-06-25 17:22
- tmax (DR & multiphasic) Helmut 2013-06-22 01:15
- Presentations of the EUFEPS meeting Helmut 2013-07-15 15:50
- ⧫ Deadline approaching ⧫ Helmut 2013-08-16 16:41
- Download comment form Helmut 2013-08-26 11:28
- Food effect Compliance 2013-08-26 12:04
- Food effect Dr_Dan 2013-08-26 16:48
- Variability (MR vs. IR) Helmut 2013-09-12 15:23
Ing. Helmut Schütz