EMA: Waiving MD study [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2020-09-09 19:26 (17 d 16:31 ago) – Posting: # 21914
Views: 1,006

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.*

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Helmut Schütz

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