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Back to the forum  2018-06-20 07:27 CEST (UTC+2h)
jag009
Hero

NJ,
2017-09-06 21:11

Posting: # 17787
Views: 1,902
 

 Enlighten me please [Regulatives / Guidelines]

Hi guys(and girls),

What is your opinion on this guidance about BE needs to be demonstrated for 2 active metabolites and not the parent? They want all three measured too.

The parent is rapidly absorbed from a 600mg dose, with a peak plasma concentration of 1.98 mg/l occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%. The parent is primarily via pathways involving N-demethylation and terminal hydroxylation... In vitro studies have shown that CYP450 3A4 is primarily responsible for the metabolism....

I don't get it. The message has always been (or almost always been) to show BE for parent if it can be accurately quantified since it is the one that gets absorbed. Someone was :party: when the document was written?

J
ElMaestro
Hero

Denmark,
2017-09-06 22:52

@ jag009
Posting: # 17788
Views: 1,632
 

 Enlighten me please

Hi Jag,

» I don't get it. The message has always been (or almost always been) to show BE for parent if it can be accurately quantified since it is the one that gets absorbed. Someone was :party: when the document was written?

I agree this is unusual. I don't know if they were partying too hard when they wrote this guideline but I can easily imagine there is a compromise of sorts involved here; perhaps someone from another FDA office (DBRUP?) wasn't convinced or was inexperienced with BE and used intuition instead of reason? Sometimes these guidelines, even though they are issued by OGD, involve a ton of inter-division compromises. I am sure that unless you find a really good reason buried in the material on the originator available via FOI the reason is going to be very hard to identify. :-|

We all have to be sheep in this situation, I guess.:-):-)

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
yicaoting
Regular

NanKing, China,
2017-09-07 02:32

@ ElMaestro
Posting: # 17789
Views: 1,619
 

 Enlighten me please

»
» We all have to be sheep in this situation, I guess.:-):-)

Wow, a pack of wolves is coming....:-D:-D
jag009
Hero

NJ,
2017-09-07 06:16

@ ElMaestro
Posting: # 17790
Views: 1,595
 

 Enlighten me please

Hi ElMaestro,

» Hi Jag,I am sure that unless you find a really good reason buried in the material on the originator available via FOI the reason is going to be very hard to identify. :-|

Even in the NDA the levels of all three analyte plus another metabolite (which FDA doesn't want to see) were reported...

Oh well...
J
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