Mahesh M ★ India, 2014-09-12 10:46 (3486 d 02:09 ago) Posting: # 13493 Views: 2,313 |
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Dear All, My concern is about Pharmacokinetic parameters for pressurised metered dose inhalers (pMDIs) EMA submission Study. As per the guideline http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003504.pdf London, 22 January 2009 Doc. Ref. CPMP/EWP/4151/00 Rev. 1 Section 6.1.1 (page no10.) “In accordance with the standard accepted methods of assessment of bioequivalence the maximum concentration (Cmax), the area under the curve (AUC) and the time to Cmax (Tmax) should be compared.” It means Bioequivalence depends on: Cmax. AUCt and Tmax? Regards |
ElMaestro ★★★ Denmark, 2014-09-12 12:14 (3486 d 00:41 ago) @ Mahesh M Posting: # 13494 Views: 1,987 |
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Hi Mahesh M, ❝ It means Bioequivalence depends on: Cmax. AUCt and Tmax? Yes. Generally bioequivalence depends on those three metrics and other stuff, but you are not creating confidence intervals for Tmax. I agree it might not be too well worded in the guideline. The responsible person should be flogged — Pass or fail! ElMaestro |
nobody nothing 2014-09-12 12:26 (3486 d 00:29 ago) (edited by nobody on 2014-09-12 16:02) @ ElMaestro Posting: # 13495 Views: 1,977 |
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❝ I agree it might not be too well worded in the guideline. The responsible person should be flogged I can help you out, it's frequently on my way — Kindest regards, nobody |
Mahesh M ★ India, 2014-09-16 09:57 (3482 d 02:58 ago) @ ElMaestro Posting: # 13514 Views: 1,786 |
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Hi ElMaestro, ❝ Yes. Generally bioequivalence depends on those three metrics and other stuff, but you are not creating confidence intervals for Tmax. Then how we compare the Tmax as BE criteria? Why Tmax is selected as Primary criteria for estimation BE for pressurised metered dose inhalers (pMDIs)? Thanks and regards M |
ElMaestro ★★★ Denmark, 2014-09-16 10:45 (3482 d 02:10 ago) @ Mahesh M Posting: # 13515 Views: 1,826 |
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Hi Mahesh M, ❝ Then how we compare the Tmax as BE criteria? Descriptive statistics + commentary + perhaps Wilcoxon's signed rank. For beta2 agonists Tmax is sometimes-often on the first or second sample and thus not well characterised by the sampling. It is difficult to plan your way out of it. ❝ Why Tmax is selected as Primary criteria for estimation BE for pressurised metered dose inhalers (pMDIs)? "Feature, not bug." I wish. — Pass or fail! ElMaestro |
Helmut ★★★ Vienna, Austria, 2014-09-16 11:21 (3482 d 01:34 ago) @ Mahesh M Posting: # 13517 Views: 1,770 |
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Hi Mahesh, ❝ Why Tmax is selected as Primary criteria for estimation BE for pressurised metered dose inhalers (pMDIs)? If you are suffering from asthma and/or COPD, wouldn’t you say that tmax matters? BTW, when the NfG was developed, nonparametric statistics were not as taboo in the EU as they are now. CPMP/EWP/QWP/1401/98 states: Statistical evaluation of tmax only makes sense if there is a clinically relevant claim for rapid release or action […]. The non-parametric 90% confidence interval for this measure of relative bioavailability should lie within a clinically determined range. Don’t ask me for acceptance range(s).— 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 |