Bioequivalence and Bioavailability Forum

Dear All,

In the draft guidline for Lansoprazole (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm086284.pdf) it is mentioned that
"The within-subject variability of the reference product is determined in a 3-way modified replicate-design study in which the reference product is given twice and the test product is given once".

Now my question is what is meant by 3-way modified replicate-design and how does it differs from usual 2 treatment, 2 sequence, 3 period replicate design (TRT/RTR) recommended by FDA.

Can we use 2 treatment, 3 sequence, 3 period replicate design i.e RTR/TRR/RRT. Wheather this design will be acceptable to FDA or not and Please also tell me if above mentioned design is balanced or not.

By using above mentioned replicate design can we get the Intra CV for reference and use it for Reference scaling average bioequivalence apporach.

Thanks for ur replies in advance.