Bioequivalence and Bioavailability Forum

Dear Pravin,

the EMA guideline, page 17 gives you the formula:

[L,U] = exp(+k*sw)

with k=0.760 and s_w the within-subject standard deviation of error.
Just fire up your pocket calculator (hopefully it has a scientific mode with the exp, log and sqrt functions ).

Use the well known formula
  CV(%)=100*sqrt(exp(s2w)-1)
reversed
  sw=sqrt(log((CV/100)2+1))
to obtain the within-subject standard deviation.

BTW:
Note that for CV > 50% the formula has to be used with CV=50% (giving you 69.84 ... 143.19%) and for CV<30% with CV=30% (giving you 80.00 ...125.00%).
Note further that you have to use a replicate design and prove that the within-subject CV for the reference has to be >30%.
Note third that the widened acceptance range only apply to Cmax, not to AUC.

BTW2: If you don't own a scientific pocket calculator (with all that ominous log, exp and sqrt) here the results of using R as pocket calculator:
CV <- 46
round(100*exp(c(-1,1)*0.760*sqrt(log((CV/100)^2+1))),2)
[1]  71.68 139.51

Hope this makes sense for you.