Bioequivalence and Bioavailability Forum

Dear Mr John,

❝ Intrasubject CV of the test product being much higher than that of the reference product.

In my experience, I encountered 1 out 10 products showed higher Intrasubject CV for test formulation when compared to ISCV of reference formulation.

Dear John
You have to distinguish between variability due to Drug Product (inactive ingredient effects, manufacturing effects) and variability due to Drug Substance (variable absorption rate, extent, low bioavailability, low aqueous solubility, acid lability and most important extensive pre-systemic metabolism). Therefore in this case it would be also interesting to compare the inter-subject variability. In general the development of the test product is more advanced and the variability due to Drug Product is less.
Kind regards
Dan

Dear Jag
My experience
For simple IR products
BCS class-1 and III: very less (~none, only shock we gor once was for BUSPIRONE where Intra subject CV was 38% and inter subject CV was 80%)
BCS class-II and IV: ~50% case (mainly beause of variable ingredient effects, manufacturing process, variable rate and extentof absorption etc etc)

For MR/ER/PR products
Variability was observed in ~50 percent case inter-subject variability was higher mainly because of he design of test product.