Bioequivalence and Bioavailability Forum

Dear M,

please look here first.

❝ The US high fat breakfast as required by the FDA in fed studies is quite a

❝ stomach-full for us Europeans (female study subjects in particular find it

❝ hard to finish).

Full ACK. See also this post.

❝ How much of the breakfast must be consumed to be eligible? Is it

❝ acceptable to eat say 60% or 75%?

I've seen protocols were the amount of food (of course not the composition) was different for males/females. All these studies were European ones (not used in NDA/ANDAs).
If you run into the situation that a volunteer capitulated in the first period - you may give it a try: write down a protocol deviation and serve a (reduced) amount in the second period. This is only valid for a BE study in the fed state. If happening in the second period or a fed/fasting study, you are out of luck.

❝ How important is it to weigh each constituent (bacon, waffles etc.)?

I wouldn't do that. You would end up with messy scales, etc. There's a lot of literature about the composition of food out there (just check a pack of toast in the local supermarket - there's a lot printed on it). Even the old Geigy tables were quite informative. Just document what you have served in a simple way plus the breakdown according to FDA's guideline (fat, carbohydrates, protein)...

❝ I have heard that the FDA can be quite strict on this.

On what? Sticking to 'their' breakfast? Yes. Weighing ingredients - haven't heard of.

I once established a European substitute (until FDA's prestidigitation with 'viscosity' came in), and found it a little bit difficult to get an idea about FDA's specifications of their 'test meal', e.g.,
  2 strips of bacon (estimated with 3 g each)
  2 slices of toast (estimated with 37.5 g)
  butter (who much? estimated with 20 g)
Using energy contents for 1 g of fat (38.9 kJ) and protein/carbohydrate (17.2 kJ) I ended up with
12% (128 kcal) of protein, 29% (308 kcal) of carbohydrate, and 59% (631 kcal) of fat. So even FDA's 'test meal' does not meet their own spec's (150, 250, 500-600)...

Dear Maurice,

just came across this presentation from CDER's Forum for International Drug Regulatory Authorities (April 14 - 18, 2008):

P Chandaroy and K Dhariwal
Bioequivalence Testing in the U.S. for Generic Drug Products
Division of Bioequivalence, OGD, CDER, FDA (16 April 2008)
online resource

• Meal should contain at least 50% of kcal from
  fat and provide 800-1000 kcal in total
  
• FDA publishes a standardized meal
  description
  • Non-standardized meal is acceptable if meets
    total kcal and fat kcal criteria
    
  • FDA discourages using vegetarian meals - may not
    produce same effects as non-vegetarian meals

Practically all protocols I've seen in the last 15+ years or so, exclude vegetarians anyhow. This may not be a real problem if running a study in North America or Europe (besides the terrible amount of food), but may become an issue if performing a study in an Indian CRO (see this thread).

Hello,
Here in the middleeast, Jordan, I've come across a similar problem and we were not able to decide how much of a food intake is allowed for the subject not to consume and different subjects have different appetites. At certain times subjects tend to have little appetite for breakfast in the early morning and we're not comfortable with the quantity served. We do have differences in our meals from europe and the states which makes mimicking the meal difficult as well as too much for subjects (mainly males!). It's not ethical to force anyone to take in the whole meal ... So, in any event how would the breakfast set by the US guidance be fit for all countries as everyarea has their "Meal Traditions".
As we have no specific guidance of our own and the region recommends the FDA guidance will it indeed be enough to record deviations
thank you very much
regards