Bioequivalence and Bioavailability Forum

Dear Prasad,

OGD product specific guidance is for 2x2x4, following NTID rules (laid out in Warfarin guidance). Yes, this is a recent change, most levo generic drugs on market right now were approved with a CO study. Current OND guidance (for NDA) is 2x2x2 crossover.

Variability would be much smaller without baseline correction. For either test, baseline correction must be applied, which is subtracting the average of 3 predose measurements from all further PK samples.

Regarding the studies you found with a sample size of 50-72, that may be required if they were powering the study for the NTID test. OR, the large sample size may be used to pass a drug with a small (e.g. GMR of 1.05) bias. AFAIK the FDA doesn't get too upset over conservative sample sizes unless they are outrageous.

Hope that helps,
BF