EMA: Waiving MD study [Regulatives / Guidelines]
❝ ❝ at the end an 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 (ka ≤ kel).
❝ Could you please kindly add more explanation.
About the script or about what I’m doing here?
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 🖖🏼 Довге життя Україна!
The quality of responses received is directly proportional to the quality of the question asked. 🚮
- EMA: Waiving MD study Helmut 2020-09-09 16:21 [Regulatives / Guidelines]