Bioequivalence and Bioavailability Forum

Hi all,

The FDA individual guidance recommends doing a 4-way full replicate study for fasting, fed and sprinkle studies for Dexmethylphenidate ER capsules:

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM296744.pdf

My question to you all is that it is known that the variability is low for this drug (ISCV <30%), so why would they recommend a full replicate study? Indeed, they do not suggest reference scaling as they explicitly state that the BE criteria is the standard ABE limits of 80.00%-125.00% for the 90% CI for the partial AUCs and Cmax.

Do they recommend the full replicate design because they also want the subject-by-formulation interaction to be calculated, similar to Methylphendate ER? If so, why is this not mentioned in the Dexmethylphenidate guidance? Was it an oversight?

Any guidance or insights would be welcomed.

Regards,
BRB