Bioequivalence and Bioavailability Forum

Dear All,

dont know if this is the right category.

But here is my question, story:
We recently conducted a 2-sequence-4-period replicate study (sequences TRTR/RTRT) to show that the reference formulation is highly variable and therefore claim to use the broadened bioequivalence range of 75-133% for Cmax.
As you surely noticed this study was European.

The study was evaluated using the Proc MIXED code from Appendix E of the FDA guidance "Statistical approaches ..." 2001. Code for instance here.

So far so good. I thought.

Now we got a question from the French authority:
QUESTIONS

The company must supply the simple calculation of intra-individual variability (mean of individual experimental differences) based on experimental data, so that the results can be compared with model values obtained using the Drug2-replicate program.

Any body out there who knows to hell what they mean? Or has an idea?
Variability=mean? Simple calculation? Experimental differences?
Totally confused.

BTW: Drug2-replicate program is the name of a SAS project (couple of macros) implementing the Proc MIXED code as its heart.