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nobody nothing 2019-02-13 19:58 (2264 d 10:42 ago) Posting: # 19907 Views: 6,483 |
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Hi again! Just by chance I stumbled upon this here: https://www.ema.europa.eu/en/dabigatran-etexilate-product-specific-bioequivalence-guidance Have a look at the comments by the originator and the final guidance. OK, pH and dabigatran is an issue, but is it really sufficient that the originator writes some 15-20 lines of text (without any citation?) to introduce a rather complex study to the development of a generic? No data at all supporting this claim? And EMA just buys it? Are we back to the 1950's? Or all data trade secrets? OMG... reminds me of some witch hunt before the inquisition started to introduce some legal procedures before the death penalty was imposed. Sorry, too late for "edit", but this might be a clear case for a publication in the Journal "Well, trust us"... http://www.sciencemag.org/careers/2012/02/ive-got-your-impact-factor-right-here  Edit: normally you should have been able to edit your message ? You have 24 hours to do so. No time limit for Mods and Admins, luckily  [Ohlbe]— Kindest regards, nobody |
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ElMaestro ★★★ Denmark, 2019-02-13 23:59 (2264 d 06:41 ago) @ nobody Posting: # 19910 Views: 5,673 |
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Hi nobody, ❝ http://www.sciencemag.org/careers/2012/02/ive-got-your-impact-factor-right-here Thanks for this link. "And the Journal of Negative Results in Homeopathy is the entire field of homeopathy."  Best day ever. — Pass or fail! ElMaestro |
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Helmut ★★★   Vienna, Austria, 2019-02-14 01:24 (2264 d 05:16 ago) @ ElMaestro Posting: # 19911 Views: 5,696 |
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![[image]](img/uploaded/image101.jpg) ![[image]](img/uploaded/image7.gif) Hi ElMaestro & nobody,too bad that the Journal of Negative Results in Biomedicine ceased to be published. I like (seriously!) this one: Hammami MM, Yusuf A, Shire FS, Hussein R, Al-Swayeh R. Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs. J Negat Results Biomed. 2017;16(1):10. doi:10.1186/s12952-017-0075-2. To avoid study bias [sic], comparative bioavailability studies should be conducted in such a way that the subjects are not aware of which product (test or reference) is being administered. — 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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nobody nothing 2019-02-14 10:31 (2263 d 20:09 ago) @ Helmut Posting: # 19914 Views: 5,656 |
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Hi Hellcourage! Yeah, but the outcome of the study was, sorry to say, negative.  @TheManWithTheFence: My favourite is "The Literature" so you can say you studied thoroughly The Literature. Nobody joins nobodies furor on this EMA thing? Quite normal to you? PS: Ohlbe, you'R right, I missed the button for "Edit", simply it's normally over/under your post in any recent forum software. Sorry for that, thank'S for your service! — Kindest regards, nobody |
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Helmut ★★★ Vienna, Austria, 2019-02-14 12:37 (2263 d 18:03 ago) @ nobody Posting: # 19915 Views: 5,673 |
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Hi nobody, ❝ Yeah, but the outcome of the study was, sorry to say, negative. Quotes from:
❝ @TheManWithTheFence: My favourite is "The Literature" so you can say you studied thoroughly The Literature. Äh, wer? ❝ […] I missed the button for "Edit", simply it's normally over/under your post … As designed and described. ❝ … in any recent forum software. Last update on Feb 10th. ![[image]](https://forum.bebac.at/screenshots/MixThread.png) If you want to have the edit-link below your post, change your preference to thread view in your profile. I could move it to the top but that’s a lot of coding (up to five links for mods / admins) and nobody [pun] except you complained so far. A f**ing lot of coding to change the link to a button.I will definitely not move it from the left bar in mix view. — 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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nobody nothing 2019-02-14 14:40 (2263 d 16:00 ago) @ Helmut Posting: # 19919 Views: 5,961 |
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❝ Hi nobody, ❝ ❝ ❝ Yeah, but the outcome of the study was, sorry to say, negative. ❝ ❝ ❝ ❝ @TheManWithTheFence: My favourite is "The Literature" so you can say you studied thoroughly The Literature. ❝ ❝ Äh, wer? https://www.zdf.de/nachrichten/heute/daenemark-baut-aus-angst-vor-schweinepest-zaun-an-grenze-zu-deutschland-100.html btw. I passed by Kolding to the east recently (Autobahn full) and while riding the countryside I saw a green Birdsong beer (?) truck. Must have been pretty close to you but forgot (again) your credentials, so no unannounced inspection of computers and coffee machines... ❝ ❝ […] I missed the button for "Edit", simply it's normally over/under your post … ❝ ❝ As designed and described. ❝ ❝ ❝ … in any recent forum software. ❝ ❝ Last update on Feb 10th. ❝ ❝ ❝ I will definitely not move it from the left bar in mix view. :-p — Kindest regards, nobody |
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Helmut ★★★ Vienna, Austria, 2019-02-14 13:12 (2263 d 17:27 ago) @ nobody Posting: # 19916 Views: 5,706 |
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Hi nobody, ❝ Have a look at the comments by the originator and the final guidance. ❝ OK, pH and dabigatran is an issue, … Highly variable in fasted but not in fed state. ❝ … but is it really sufficient that the originator writes some 15-20 lines of text (without any citation?) to introduce a rather complex study to the development of a generic? No data at all supporting this claim? And EMA just buys it? Are we back to the 1950's? Aren’t you notoriously shouting “It’s the originator, stupid…”? I’m more concerned about the first footnote in the guidance * As intra-subject variability of the reference product has not been reviewed to elaborate this product-specific bioequivalence guideline, it is not possible to recommend at this stage the use of a replicate design to demonstrate high intra-subject variability and widen the acceptance range of Cmax. If high intra-individual variability (CVintra > 30 %) is expected, the applicants might follow respective guideline recommendations. meaning that one can plan for the EMA’s method of reference-scaling. Was the EMA’s PKWP not aware of the the FDA’s guidance?— 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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nobody nothing 2019-02-14 14:34 (2263 d 16:06 ago) @ Helmut Posting: # 19918 Views: 5,711 |
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❝ Highly variable in fasted but not in fed state. Hm, here we talk about solubility over relevant pH range. Only good solubility in acidic range, but... see Samant, 2018 on ribociclib. Solubility in aqueous media is only half the story. ❝ Aren’t you notoriously shouting “It’s the originator, stupid…”? Could you elaborate on this. No clue what this might mean. If you want a duel, choose your weapon  ❝ I’m more concerned about the first footnote in the guidance * As intra-subject variability of the reference product has not been reviewed to elaborate this product-specific bioequivalence guideline, it is not possible to recommend at this stage the use of a replicate design to demonstrate high intra-subject variability and widen the acceptance range of Cmax. If high intra-individual variability (CVintra > 30 %) is expected, the applicants might follow respective guideline recommendations. meaning that one can plan for the EMA’s method of reference-scaling. Was the EMA’s PKWP not aware of the the FDA’s guidance?Narrow therapeutic range... maybe in the USA. In the EU there are no mass tort trials... What buys you the widening for Cmax, when both parameters are highly variable?  — Kindest regards, nobody |
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Helmut ★★★ Vienna, Austria, 2019-02-14 14:52 (2263 d 15:48 ago) @ nobody Posting: # 19920 Views: 5,512 |
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Hi nobody, ❝ ❝ Aren’t you notoriously shouting “It’s the originator, stupid…”? ❝ Could you elaborate on this. No clue what this might mean. See there. ❝ If you want a duel, choose your weapon ❝ Surströmming? ❝ ❝ I’m more concerned about the first footnote in the guidance […]. Was the EMA’s PKWP not aware of the the FDA’s guidance? ❝ ❝ Narrow therapeutic range... maybe in the USA. In the EU there are no mass tort trials... I don’t like the idea that someone widens the limits for this stuff. ❝ What buys you the widening for Cmax, when both parameters are highly variable? Business as usual in all jurisdictions following the EMA’s strange approoach (i.e., WHO; ASEAN States, Australia, Brazil, Egypt, the Russian Federation, the Eurasian Economic Union, New Zealand). At least the WHO initiated a pilot phase for scaling the AUC. For HC widening the limits for AUC is acceptable (no big deal for Cmax; only the PE within 80.0–125.0%). — 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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nobody nothing 2019-02-14 16:01 (2263 d 14:38 ago) @ Helmut Posting: # 19921 Views: 5,540 |
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❝ ❝ ❝ Aren’t you notoriously shouting “It’s the originator, stupid…”? ❝ ❝ Could you elaborate on this. No clue what this might mean. ❝ ❝ See there. yeah, but you need irony tags in here,don'T you? ❝ ❝ If you want a duel, choose your weapon ❝ ❝ ❝ ❝ Surströmming? No chemical weapons. ❝ ❝ ❝ I’m more concerned about the first footnote in the guidance […]. Was the EMA’s PKWP not aware of the the FDA’s guidance? ❝ ❝ ❝ ❝ Narrow therapeutic range... maybe in the USA. In the EU there are no mass tort trials... ❝ ❝ I don’t like the idea that someone widens the limits for this stuff. ...maybe we will never see such generics in our lifetime. Wait and see... — Kindest regards, nobody |
Ing. Helmut Schütz