Mahesh M
★    

India,
2014-09-12 10:46
(3486 d 02:09 ago)

Posting: # 13493
Views: 2,313
 

 pressurised metered dose inhalers (pMDIs) [Regulatives / Guidelines]

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
 

 pressurised metered dose inhalers (pMDIs)

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 :-D

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
 

 pressurised metered dose inhalers (pMDIs)

❝ I agree it might not be too well worded in the guideline. The responsible person should be flogged :-D


I can help you out, it's frequently on my way :-D

Kindest regards, nobody
Mahesh M
★    

India,
2014-09-16 09:57
(3482 d 02:58 ago)

@ ElMaestro
Posting: # 13514
Views: 1,786
 

 pressurised metered dose inhalers (pMDIs)

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
 

 pressurised metered dose inhalers (pMDIs)

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
★★★
avatar
Homepage
Vienna, Austria,
2014-09-16 11:21
(3482 d 01:34 ago)

@ Mahesh M
Posting: # 13517
Views: 1,770
 

 pMDIs: Tmax

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).

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