Bioequivalence and Bioavailability Forum

Dear all!

We know from this rather lengthy thread that k 0.760 leads to a (small) discontinuity of the acceptance range. Maybe that’s the reason the GL states

Highly variable drug products (HVDP) are those whose intra-subject variability for a parameter is larger than 30%. […] For the acceptance interval to be widened the bioequivalence study must be of a replicate design where it has been demonstrated that the within-subject variability for C_max of the reference compound in the study is >30%.

(my emphases)

Note the subtle difference CV >30% to the one generally used (CV ≥30%). From the table in the GL, it’s clear that 0.760 – rather than ln(1.25)/sqrt(ln(0.3²+1)) – should be used. Should we round another two times (both the CL and the acceptance limits to two decimal places) – in analogy to Section 4.1.8?