Bioequivalence and Bioavailability Forum

Hi all,

I regularly look at bioanalytical validations where between-batch (between-run etc) precision is addressed.
Typically, the CRO or lab will study m batches (runs) with n injections of a given QC level. You can think of it as m vectors of length n containing concentration estimates.

Between-batch precision is typically evaluated by calculating the SD across all n x m values, then dividing by the grand mean, and that seems to generally pass a regulatory inspection.
But that isn't really between-batch precision, by any reasonable definition of between-batch, in my opinion. It is precision without regard to within and between, because the calculation sd does not take into account where the values came from.

If we were to truly evaluate between-batch precision (i.e. what is the CV of our estimate between batches) then we could study m batches, extract the m means and do precision on the means. The reason it isn't done in practice is apparently that it is too complicated or labour intensive (we'd need more than the usual m=3).

If we wish to accept companies just doing sd from the m x n values and using this to qualify the validation then we shouldn't call it between-batch precision. Or alternatively, if we wish to insist on working on an experiment called between-batch precision then we should calculate it differently.

That's my totallly unqualified opinion on this mighty pleasant Friday morning. I only had 1 L of covfefe so far so pardon me if any part of this post can resemble grumpiness.