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Jay ☆ India, 2013-09-16 17:39 (4664 d 02:55 ago) Posting: # 11499 Views: 4,492 |
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Hi, As we know the draft guidelines have been published for modified release dosage forms but its not finalised. So if one conducts BE study for modified release now so they have to follow current guidelines for BE Study of EMA? If Yes then suppose the draft guidelines get finalised before submission, then will it raise query? Otherwise can we add statement in the protocol regarding that? As per current guideline, in SD Cmax & AUCt as primary while in MD, Cminss, Cmaxss and AUCtau as primary. Shall one add pAUC in secondary parameter considering the draft guidelines? Kindly guide. |
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jag009 ★★★ NJ, 2013-09-16 19:30 (4664 d 01:05 ago) @ Jay Posting: # 11501 Views: 3,838 |
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Hi, I don't know how EMA run their business. For FDA we always go with the draft guidance even though it's not finalized because
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Helmut ★★★   Vienna, Austria, 2013-09-17 15:35 (4663 d 05:00 ago) @ Jay Posting: # 11504 Views: 3,801 |
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Hi Jay, ❝ […] If Yes then suppose the draft guidelines get finalised before submission, then will it raise query? (1) Yes and (2) maybe. ❝ Otherwise can we add statement in the protocol regarding that? Sure. The more you deviate from the current NfG, the more complicated it gets. ❝ As per current guideline, in SD Cmax & AUCt as primary while in MD, Cminss, Cmaxss and AUCtau as primary. ❝ ❝ Shall one add pAUC in secondary parameter considering the draft guidelines? Why not? The problems start with the truncation time point (which has to be prespecified). I guess I will not have been the only one objecting against τ/2. The first pAUC might be highly variable (though widening of the acceptance range might be possible if the study was performed in a replicate design). If in doubt, go for a scientific advice. — 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 |
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Jay ☆ India, 2013-12-23 12:00 (4566 d 07:34 ago) @ Helmut Posting: # 12095 Views: 3,355 |
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Dear John and Helmut, Thank you for your reply. ❝ Why not? The problems start with the truncation time point (which has to be prespecified). I guess I will not have been the only one objecting against τ/2. The first pAUC might be highly variable (though widening of the acceptance range might be possible if the study was performed in a replicate design). If in doubt, go for a scientific advice. Any idea about which truncation point to be considered for pAUC? As pAUC is considered to be more variable as compared to Cmax and AUC. Thus should Sample Size be considered accourdingly? And if it is to be considered more subjects may be required. And for pAUC which literature should we consider for calculation of Sample Size? Regards, Jay |
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Helmut ★★★ Vienna, Austria, 2013-12-23 14:54 (4566 d 04:41 ago) @ Jay Posting: # 12096 Views: 3,408 |
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Hi Jay, ❝ Any idea about which truncation point to be considered for pAUC? Until the GL gets finalized, we are fishing in foul water. The FDA clearly prefers a clinical justification (based on PD), whereas the EMA seems to prefer PK. However, in my studies I succeeded with the former. As said before, go for a [e]scientific[/e] regulatory advice. Carry clinical data as ammunition with you. Don’t simply ask them. One company doing so went back home from London with AUC0–2 for methlyphenidate in their backpack.  ❝ As pAUC is considered to be more variable as compared to Cmax and AUC. Likely. ❝ Thus should Sample Size be considered accourdingly? Sure. You have to show BE for pAUC as well. ❝ […] more subjects may be required. Yes. ❝ […] for pAUC which literature should we consider for calculation of Sample Size? The only published data on pAUCs are for methlyphenidate and zolpidem. I’m afraid you have to perform a pilot study – if you assume high variability, in a replicate design. — 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 |
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Jay ☆ India, 2013-12-23 15:54 (4566 d 03:40 ago) @ Helmut Posting: # 12098 Views: 3,353 |
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Thanks Helmut for the reply. Hope the Guideline gets published soon and provides clarity for truncation point of pAUC. If we conduct BE as per draft MR GL, can we submit it even if new MR GL is still in draft? |
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Helmut ★★★ Vienna, Austria, 2013-12-23 16:41 (4566 d 02:53 ago) @ Jay Posting: # 12099 Views: 3,356 |
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Hi Jay, ❝ Hope the Guideline gets published soon and provides clarity for truncation point of pAUC. I expect only a general statement in the MR GL. Maybe we will see particular truncation time-points in the product-specific guidances. However, never follow GLs unreflected. Science should always be the basis — 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 |
Ing. Helmut Schütz