Bioequivalence and Bioavailability Forum

HI Sereng!

❝ (1) If you conduct a full replicate crossover design BE study (T x 2, R x 2, e.g., TRTR|RTRT) is there any sample size efficiency (fewer patients required) with ABE analysis or is it no different (in terms of sample size) than a non-replicate crossover design BE study (T x1, R x 1) with ABE analysis.

The number of observations will be same but the sample size will be half in fully replicate design compared to standard CO study.

❝ (2) For demonstrably HVD (WSV >30%), why do some product specific guidance for ANDA suggest (or allow) full replicate designs and others do not mention this approach?

For HVD, the fully replicate/partial replicate can be helpful for widening of 90% CI limit based on regulatory agency for particular PK parameters. Ethically, due to widening of 90% CI, the sample size will be less than if it has be to standard limit of 80-125%.

❝ (3) For demonstrably HVD (WSV >30%), why do some Clinical Divisions object to use of full replicate design studies in 505(b)(2) NDAs?

Not aware of any. Can you share the link?

Regards,
Divyen