mmw ☆ India, 2017-07-14 16:50 (2268 d 01:35 ago) Posting: # 17548 Views: 9,212 |
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Dear all, EMA adopted a new batch of product specific guidances. Published on 10/07/2017: Crizotinib Elvitegravir / cobicistat / emtricitabine / tenofovir disoproxil Elvitegravir Emtricitabine, rilpivirine, tenofovir, disoproxil Vortioxetine Thanks MMW |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-07-28 14:40 (2254 d 03:46 ago) @ mmw Posting: # 17620 Views: 8,248 |
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Dear all, a new set of product-specific guidances was adopted by CHMP for public consultation on 22 June (published on 28 July [1–4], 3 August [5–7]). Deadline for comments: 31 October.
— 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 |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-08-03 19:47 (2247 d 22:38 ago) @ Helmut Posting: # 17660 Views: 8,326 |
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Dear all, In the product-specific guidance for Dimethyl fumarate gastro-resistant capsules 120 mg and 240 mg we find: Main pharmacokinetic variables: I beg your pardon, tlag‽ For delayed release products any change in tlag directly translates into a shifted tmax (see this presentation, slides 53–58). Whilst the latter PK metric is generally already covered by rich sampling (in order to “catch” Cmax) this is not the case for tlag. I don’t get it. — 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 |
BRB ☆ Canada, 2017-12-20 17:25 (2109 d 00:01 ago) @ Helmut Posting: # 18067 Views: 7,193 |
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Hello Helmut and others, I don't get it either regarding the evaluation of tlag. How would one show that there is, "Comparable median and range for tlag" between the test and reference? Non-parametric test? Any feedback would be appreciated. Thanks! BRB |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-12-21 14:28 (2108 d 02:57 ago) @ BRB Posting: # 18072 Views: 7,191 |
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Hi BRB, ❝ How would one show that there is, "Comparable median and range for tlag" between the test and reference? By a combination of ![]() ❝ Non-parametric test? Unlikely… Let’s actuate our time machine and have a look what was / is suggested for tmax and tlag.
For my current practice see this post and why assessing the range is crazy, this one. When it comes to tlag I hope that this PK metric will be dropped in the final version of the dimethyl fumarate guidance. Try this R-code to see how strangely the difference in ranges (of T and R) might behave:
— 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 |
nobody nothing 2017-12-21 15:17 (2108 d 02:09 ago) @ Helmut Posting: # 18073 Views: 7,130 |
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...backdoor? These are REALY ugly times we life in... — Kindest regards, nobody |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-12-21 15:43 (2108 d 01:43 ago) @ nobody Posting: # 18074 Views: 7,362 |
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Hi nobody, ❝ ...backdoor? These are REALY ugly times we life in... IMHO, just crazy: This is the comment I’ve send to the EMA on 31 October: For gastric-resistant formulations any [sic] difference in tlag is reflected in tmax as well. In other words: Any shift in tlag will lead to exactly the same shift in tmax.
Proposed change (if any): — 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 |
nobody nothing 2017-12-21 16:18 (2108 d 01:07 ago) @ Helmut Posting: # 18076 Views: 7,129 |
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...somebody had a look at the ADRs (mostly upper GI-tract-related, therefore the gastroresistant formulation) and said, hey, we have to "quantitate" the quality of the gastroresistant part of the formulations. Let's do tlag! afaik the SmPC recommends application in fed state, due to better tolerability. The EMA guideline gives no recommendation re. fasted/fed?! On the other hand: Modified release with one single-dose study only? — Kindest regards, nobody |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-12-21 16:41 (2108 d 00:44 ago) @ nobody Posting: # 18077 Views: 7,346 |
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Hi nobody, ❝ ...somebody had a look at the ADRs (mostly upper GI-tract-related, therefore the gastroresistant formulation) and said, hey, we have to "quantitate" the quality of the gastroresistant part of the formulations. Let's do tlag! Splendid idea! Why not an early partial AUC? ❝ afaik the SmPC recommends application in fed state, due to better tolerability. Yep. ❝ The EMA guideline gives no recommendation re. fasted/fed?! Strange. The MR-GL suggests for delayed release multiple unit formulations (if SmPC recommends intake under fed conditions): SD fasting and fed. ❝ On the other hand: Modified release with one single-dose study only? Do you mean why no MD study? That’s consistent with the MR-GL. — 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 |
nobody nothing 2017-12-21 16:57 (2108 d 00:28 ago) @ Helmut Posting: # 18078 Views: 7,135 |
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...no, more related to fasted/fed... ![]() — Kindest regards, nobody |