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jag009 ★★★ NJ, 2018-09-10 20:41 (2198 d 11:08 ago) Posting: # 19257 Views: 6,155 |
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Hi all, One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right? Thanks John Edit: Category changed; see also this post #1. [Helmut] |
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ElMaestro ★★★ Denmark, 2018-09-11 00:52 (2198 d 06:57 ago) @ jag009 Posting: # 19258 Views: 5,346 |
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Hi jag, ❝ One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right? Where does that concept come from? And could you put more words to it? Also, I am thinking a plateau is something which is hard to debate in a purely measurable way. Muy confundido  — Pass or fail! ElMaestro |
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jag009 ★★★ NJ, 2018-09-12 02:00 (2197 d 05:49 ago) @ ElMaestro Posting: # 19262 Views: 5,121 |
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❝ ❝ One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right? ❝ ❝ Where does that concept come from? And could you put more words to it? ❝ Also, I am thinking a plateau is something which is hard to debate in a purely measurable way. ❝ ❝ Muy confundido NOT me! My boss said so... I was wondering too. Does it matter if the drug is an ER or IR? Thx John |
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Obinoscopy ★ USA, 2018-09-11 22:21 (2197 d 09:28 ago) @ jag009 Posting: # 19260 Views: 5,203 |
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❝ One question related to f2 computation... According to guidance you only include one pt after 85 % release. Yes. ❝ But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right? I don't think so. Once 85% dissolution has been achieved, then we can calculate for f2. Was told 85% is a sacred clinical number (don't ask who told me  ). Was told once 85% of a drug dissolves within the expected time the drug gets to the intestine, then it is very bioavailable. Whatever happens beyond the 85% is just additional info which isn't critical. Based on this, I think 85% is the determinant. Only if 85% is not achieved then we now check when plateau is reached. Not sure though. Perhaps I'm mixing up biowaivers dissolution with other form of dissolution studies. — Scopy |
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jag009 ★★★ NJ, 2018-09-12 02:01 (2197 d 05:47 ago) @ Obinoscopy Posting: # 19263 Views: 5,131 |
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Hi, ❝ Based on this, I think 85% is the determinant. Only if 85% is not achieved then we now check when plateau is reached. ❝ ❝ Not sure though. Perhaps I'm mixing up biowaivers dissolution with other form of dissolution studies. Thanks but the person who told me insisted that it is the correct way john |
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Obinoscopy ★ USA, 2018-09-12 02:38 (2197 d 05:11 ago) @ jag009 Posting: # 19264 Views: 5,089 |
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❝ Thanks but the person who told me insisted that it is the correct way I just checked the WHO interchangeability guideline, it states: "a maximum of one-time point should be considered after 85% dissolution of the reference (comparator) product has been reached; in the case where 85% dissolution cannot be reached...the dissolution should be conducted until an asymptote (plateau) has been reached" I don't know what the USFDA GLs say though. I guess person who told you has a lot of explaining to do. I for one, am very interested in his explanation. Regards, — Scopy |
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Helmut ★★★   Vienna, Austria, 2018-09-12 03:01 (2197 d 04:47 ago) @ Obinoscopy Posting: # 19265 Views: 5,017 |
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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 |
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jag009 ★★★ NJ, 2018-09-12 22:35 (2196 d 09:13 ago) @ Obinoscopy Posting: # 19280 Views: 5,059 |
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Hi, ❝ I don't know what the USFDA GLs say though. ❝ I guess person who told you has a lot of explaining to do. I for one, am very interested in his explanation. But if you do end up computing f2 using all pts? What's the harm in that? Isn't it better to conclude based on a complete profile? (meaning stop when plateau is evident. Of course this term plateau is kinda of objective. Example: Time: 1,2,3,4,6,8,10,12 R: 27,42,54,62,76,86,92,96 T: 34,51,64,73,87,94,98,99 If we go by the definition out there then you would cut off at 8 hours. But if you compute f2s at 8 hrs cutoff vs 12 hrs then the 8 hr cutoff f2 will fail (<50). At 8 hrs the profile isn't really complete (visually). Thank John |
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ElMaestro ★★★ Denmark, 2018-09-13 00:02 (2196 d 07:47 ago) @ jag009 Posting: # 19281 Views: 5,026 |
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Hi jon, ❝ But if you do end up computing f2 using all pts? What's the harm in that? Isn't it better to conclude based on a complete profile? (meaning stop when plateau is evident. Of course this term plateau is kinda of objective. No, actually there could be a good reason not to do that. Consider very early and very late time points. Even if the two curves are shifted, the very early points could be close to zero dissolution, and the very late time points could close to maximum dissolution. for both. Inclusion of (many of) those points in a quantitative comparison will skew the conclusion towards similarity. You absolutely want to assure that you are capturing mainly the "steep" part of the curves. The sexy stuff in dissolution happens right where you are neither very early nor very late. A comparison of plateau levels say nothing about product performance but just about relative maximum dissolution. — Pass or fail! ElMaestro |
Ing. Helmut Schütz