Bioequivalence and Bioavailability Forum

❝ [...] set your upper limit of the BMI to e.g., 29, Ethics Committee is

❝ asking for reference of any published study where this upper limit of

❝ BMI has been considered or any guidelines allowing the same.

• I've seen hundreds (!) of studies in healthy young subjects (!), where the upper limit of the BMI was set to 27 kg/m² and also hundreds where the limit was set to 29 kg/m².
  
• Are your statements about the EC an assumption?
  
• Again: in a cross-over design every subject acts as it's own reference. What are your concerns about a higher BMI? Can you explain how a higher BMI would change the T/R-ratio (BE!) in a particular subject? Maybe you are mixing up inter- and intra-subject variability. A highly lipohilic drug may show lower plasma concentrations (and even a longer terminal half life) in a subject with a high BMI compared to a subject with a low BMI, but the T/R will be the same.
  
• If the EC is always asking for published BE studies to approve a new one, you should consider changing location or going out of business...
  
• It's the job of the investigator to defend the study at the EC and explain the chosen design. There's an abundance of literature demonstrating that BMI increases with age, and BE is an intra-subject comparison. So it's up to you.