Bioequivalence and Bioavailability Forum

Dear Pash!

❝ 1. As per current EU guideline statistical evaluation of Tmax is not required, if our drug is not rapid release formulation. In old guidance it was mentioned as “if appropriate to the evaluation the analysis technique for Tmax should be non-parametric and should be applied to un-transformed data”.

You are mixing things up. Both quotes come from IR guidelines.

A statistical evaluation of t_max is not required. However, if rapid release is claimed to be clinically relevant and of importance for onset of action or is related to adverse events, there should be no apparent difference in median t_max and its variability between test and reference product.

• Comparison only required if clinically relevant:
  □ No apparent difference in median t_max between test and reference product.
  □ No apparent difference in its variability.

BTW, in my studies I run nonparametrics on t_max essentially ignoring the guideline.

❝ Is it required to performed statistical evaluation of Tmax in studies conducted after implementation of new guideline?

No. But don’t ask me how to assess the variability if required. F**ing boxplots again (like in the assessment of outliers in replicate studies)?

❝ Our formulation is not rapid release formulation.

So what is it exactly? CR, DR, multiphasic, pulsatile,…? T_max is not mentioned in the MR guidance from 1999. Not even for MR formulations where rapid onset is of importance t_max is required (see here).

❝ Should we have to analyze (bioanalysis) plasma samples of that dropped/withdraw subject(s)?

Yes.