jag009
★★★

NJ,
2015-03-19 17:16
(3297 d 12:59 ago)

Posting: # 14580
Views: 3,931
 

 No Food effect on NDA (505(b)1 or 2) [Regulatives / Guidelines]

Hi all,

Question for NDAs (FDA or EMA)... If you want to claim no food effect on your new product, is it base on the 90% CI for Cmax and AUCs from a food effect study? I had a previous submission with a product having Fed/Fasting Cmax ratio of 1.22 but the 90% CI was beyond 80-125% (AUC was fine on both Ratio and 90%CI) and FDA granted us no food effect. I asked people about this and they said one needs to pass the 90% CI in order to declare no food effect...

Thanks
John
krish85
☆    

India,
2015-03-24 06:44
(3292 d 23:30 ago)

@ jag009
Posting: # 14602
Views: 3,196
 

 No Food effect on NDA (505(b)1 or 2)

Refer the link below:

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126833.pdf

On page 7 of section V, it is mentioned that,
A food-effect study involving administration of [the drug product] to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax was decreased 15% while the AUC remained unchanged. This decrease in exposure is not clinically significant, and therefore [the drug] could be taken without regards to meals.

If drug's AUC is not affecting significantly under fed condition and/or it is not producing any meaningful pharmacodynamic changes than, you can take the drug with or without food.


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]
luvblooms
★★  

India,
2015-03-24 11:06
(3292 d 19:08 ago)

@ krish85
Posting: # 14607
Views: 3,193
 

 No Food effect on NDA (505(b)1 or 2)

Dear Krish

❝ On page 7 of section V, it is mentioned that,

A food-effect study involving administration of [the drug product] to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax was decreased 15% while the AUC remained unchanged. This decrease in exposure is not clinically significant, and therefore [the drug] could be taken without regards to meals.


You missed the point. What you mentioned is an example of this long paragraph which clearly states that

For an NDA, an absence of food effect on BA is not established if the 90 percent CI for the ratio of population geometric means between fed and fasted treatments, based on log-transformed data, is not contained in the equivalence limits of 80-125 percent for either AUC0-inf (AUC0-t when appropriate) or Cmax. When the 90 percent CI fails to meet the limits of 80-125 percent, the sponsor should provide specific recommendations on the clinical significance of the food effect based on what is known from the total clinical database about dose-response (exposure response) and/or pharmacokinetic-pharmacodynamic relationships of the drug under study. The clinical relevance of any difference in Tmax and tlag should also be indicated by the sponsor. The results of the food-effect BA study should be reported factually in the CLINICAL PHARMACOLOGY section of the labeling and should form the basis for making label recommendations (e.g., take only on an empty stomach) in the DOSAGE AND ADMINISTRATION section of the labeling. ”

If no CI limit between 80-125% you need to do exposure response study/PD study which would not be that easy

Dear John

The only logic I can think of your product getting approved is that FDA might have some data on the product which shows that differences in Cmax will not have any impact on safety and efficacy profile.
It is just a guess ;-)

~A happy Soul~
Helmut
★★★
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Homepage
Vienna, Austria,
2015-03-24 11:39
(3292 d 18:36 ago)

@ luvblooms
Posting: # 14608
Views: 3,128
 

 No Food effect on NDA (505(b)1 or 2)

Hi Luv,

❝ You missed the point.

❝ In the paragraph just above the one you mentioned, it is clearly stated that […]



Exactly! Just saw a presentation by FDA’s Mehul Mehta. The food effect study should be powered for the 80–125% acceptance range and 90% CIs. If lacking food effect is not shown, the efficacy/safety data (from phase III) will be reviewed by the FDA in order to assess whether the observed difference is considered clinically relevant (depending on that the wording in the label will differ). Having data in both fasting/fed state in the phase III programme greatly helps. The FDA doesn’t expect an additional „PD food effect study“.

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luvblooms
★★  

India,
2015-03-24 12:08
(3292 d 18:07 ago)

@ Helmut
Posting: # 14610
Views: 3,138
 

 No Food effect on NDA (505(b)1 or 2)

Hi Helmut


❝ Exactly! Just saw a presentation by FDA's Mehul Mehta. The food effect study should be powered for the 80-125% acceptance range and 90% CIs. If lacking food effect is not shown, the efficacy/safety data (from phase III) will be reviewed by the FDA in order to assess whether the observed difference is considered clinically relevant (depending on that the wording in the label will differ). Having data in both fasting/fed state in the phase III programme greatly helps. The FDA doesn't expect an additional „PD food effect study“.


Thanks for further clarifying it.

~A happy Soul~
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