Jay
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India,
2015-06-02 14:43
(3222 d 23:51 ago)

Posting: # 14895
Views: 8,432
 

 EMA Steady State Fed Study breakfast [Regulatives / Guidelines]

Dear All,

As per EMA GL on MR products, for the Steady state studies of MR products under fed condition, the meal to be given prior to dosing is mentioned as "standard Meal", while in single dose fed studies it is stated as high fat meal.

So how should standard meal be around total of 700-800 kcal meal!!

Please provide your views on the same

Regards,
Jay
jag009
★★★

NJ,
2015-06-19 22:57
(3205 d 15:37 ago)

@ Jay
Posting: # 14967
Views: 7,107
 

 EMA Steady State Fed Study breakfast

Shouldn't it be the same meal as in the single dose fed study? I recall when I did SS fed study for FDA, the meal was high fat breakfast. I don't think EMA would use different meals.

John
Helmut
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Vienna, Austria,
2015-06-23 02:25
(3202 d 12:09 ago)

@ jag009
Posting: # 14969
Views: 7,091
 

 EMA Steady State Fed Study breakfast

Hi John,

❝ Shouldn't it be the same meal as in the single dose fed study?


Nope. Jay understood the GL correctly (Section 6.1.1.2):

[…] steady-state studies should be performed under the con­di­tions concerning concomitant food intake recommended in the SmPC for the originator product. If the SmPC states that the product has to be taken in fed condition only the study should be performed in fed con­di­tions (standard meal) including the day of profiling. If the SmPC states that the product should be taken in fasted state or irrespective of food intake the studies should be per­form­ed in fasted conditions. Fasting conditions in a multiple dose study needs to be adapted to realistic situations, i.e. morning administration requires a 10 hour fasting interval whereas for all other administrations 4 hour fasting prior to administration is sufficient. Fasting after each administration should be defined as 2 hour minimum.


❝ I recall when I did SS fed study for FDA, the meal was high fat breakfast.


FDA ≠ EMA. :-D

❝ I don't think EMA would use different meals.


Cough… At conferences (Barcelona 2011, Bonn 2013) we had lengthy discussions about this issue. If I recall it correctly, a vast majority of attendees followed these arguments:
  • The high-fat, high-calory meal is known to be problematic – especially for females. Serving this stuff during the entire saturation phases is not realistic. :vomit:
  • A compromise would be normal meals during saturation phases and the same (high-fat) meal like in the single dose study on profile days.
Why EMA decided to suggest normal meals throughout the entire study remains a mystery. We are all waiting since last November for the PKWP’s comments to be published. Promised for “the next week” a couple of times (Amsterdam March, London April, Budapest May)…

Bonus question: Design a multiple dose fed state study of a delayed release product administered thrice a day – compliant with EMA’s last two sentences quoted above.

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nobody
nothing

2015-06-23 11:11
(3202 d 03:23 ago)

@ Helmut
Posting: # 14970
Views: 6,956
 

 EMA Steady State Fed Study breakfast

1. dose 08:00
2. dose 13:00
3. dose 20:00

no one is taking "tid" every 8 h, except for antivirals, I guess… :-)

three times daily the "high-fat breakfast" during saturation and profiling: 98% drop-out? — :-(

Kindest regards, nobody
mmw
☆    

India,
2017-08-23 12:00
(2410 d 02:34 ago)

@ Helmut
Posting: # 17743
Views: 4,959
 

 EMA Steady State Fed Study breakfast

Dear Helmut,

A compromise would be normal meals during saturation phases and the same (high-fat) meal like in the single dose study on profile days.[/list]Why EMA decided to suggest normal meals throughout the entire study remains a mystery. We are all waiting since last November for the PKWP’s comments to be published. Promised for “the next week” a couple of times (Amsterdam March, London April, Budapest May)…


I am going through EMA's website and searching for comments on GL for modified release dosage form. But could not get it. Whether they published comments or not? Have you received it?

Presently, I am designing fed MD study for a prolonged release formulation. Should I go for normo-caloric meals (rather than high fat meal) throughout the study including profiling day. This will comply with present GL, right?

Thank you very much in advance.

MMW
Helmut
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Vienna, Austria,
2017-08-23 20:14
(2409 d 18:20 ago)

@ mmw
Posting: # 17745
Views: 4,982
 

 EMA Steady State Fed Study breakfast

Hi MMW,

❝ ❝ […] We are all waiting since last November for the PKWP’s comments to be published. Promised for “the next week” a couple of times (Amsterdam March, London April, Budapest May)…


❝ I am going through EMA's website and searching for comments on GL for modified release dosage form. But could not get it. Whether they published comments or not?


Do you really still hope that – after more than two years of broken promises – the comments will ever be published? C’mon!

❝ […] I am designing fed MD study for a prolonged release formulation. Should I go for normo-caloric meals […] throughout the study including profiling day. This will comply with present GL, right?


If (!) administration in fed state is recommended in the SmPC of the originator, yes.
If not (the SmPC allows fasting or fed), no idea. Too bad, that we don’t have the comments for clarification. In the SD study testing the food effect a high-fat high-calory meal is mandatory. What if an assessor wants the same on profile days? No idea. If you prefer to wear a belt plus suspenders, opt for a scientific regulatory advice.

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