Bioequivalence and Bioavailability Forum

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.

❝ 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.
  
• 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.