Bioequivalence and Bioavailability Forum

Hi ElMaestro

❝ ❝ If higher variability is a constrain you can always use Weibull method or MSD. EMA accept that.

❝

❝ (my coloring)

❝ Perhaps, I think those are slightly dangerous statements. Wouldn't you rather say that some assessors may accept the use of a Weibull or MSD model if you are in a sittuation where the basic discussion in 1401/98 does not pave the way forward? Technically

As per EMA BE guidance page 21 of 27, it is very clearly written that

When the ƒ₂ statistic is not suitable, then the similarity may be compared using model-dependent or model-independent methods e.g. by statistical multivariate comparison of the parameters of the Weibull function or the percentage dissolved at different time points.
Alternative methods to the ƒ₂ statistic to demonstrate dissolution similarity are considered acceptable, if statistically valid and satisfactorily justified.

❝ I guess EMA won't accept anything as assessment is done at the national agencies and there is as far as I know no guidance in place which forces any national assessor to have any specific opinion about any named dissolution model other than the moderate discussion available in 1401/98.

Will slightly disagree on that. We have submitted the similarity calculation using MSD and Weibull to some national agencies (Netherlands, Germany,UK etc) and got approvals as well. Once Netherlands authority has upfront ask as as to use other methods to show similarity as the RSDs were higher upto 20 min (product having DT of 10 min). Only trick was deciding the MSD (based on reference data) and you are good to go.