EMA: Waiving MD study [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2020-09-09 19:26 (135 d 01:14 ago) – Posting: # 21914
Views: 1,920

Hi Osama,

» » at the end an [image] script to play with.
» »
» » For any elimination half life of > 7 hours and an intended dosing interval of 24 hours it will be impossible to get the MD study waived. Red are formulations with flip-flop PK (kakel).
» Could you please kindly add more explanation.

About the script or about what I’m doing here? :-D

OK, seriously: Acc. to the EMA’s GL the MD study can be waived if AUCτ–∞ is ≤10% of AUC0–∞. Of course, in the SD study you would sample longer than τ to get a reliable estimate of λz and show that AUC0–t ≥ 80% AUC0–∞. Furthermore, you would try to show equivalence of partial AUCs.
When you develop an extended release formulation you try to slow down absorption, i.e., decrease the ka/kel-ratio – which the script does. That’s all you can do cause kel is drug-specific. In an ideal case (e.g., no absorption window) the AUC will not be affected, only Cmax will be lower and delayed. So far, so good.
But it has a nasty side effect. The early part of the AUC (until τ) will decrease and the late part increase, making waiving the MD study not possible due to the ≤10% of AUC0–∞ limit.*

Dif-tor heh smusma 🖖
Helmut Schütz

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

Complete thread:

 Admin contact
21,310 posts in 4,445 threads, 1,489 registered users;
online 3 (1 registered, 2 guests [including 2 identified bots]).
Forum time: Friday 19:41 CET (Europe/Vienna)

Statistics is, or should be, about scientific investigation
and how to do it better, but many statisticians believe
it is a branch of mathematics.    George E.P. Box

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