Bioequivalence and Bioavailability Forum

Dear all,

I have another question regarding the study design.

As per BE guideline, “A statistical evaluation of tmax 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 tmax and its variability between test and reference product.”

Now nitrofurantoin is indicated for the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures. SMPC

As per my understanding rapid release is not clinically relevant in this case (generally applied for analgesic drugs) and statistical evaluation of tmax is not required.

Now what if this test is performed and apparent difference is cited for tmax. But BE criteria Cmax and AUC fulfilled? This will lead to deficiency from the agency.

Please suggest statistical evaluation of tmax is required in this BE study or not.

Regards,
PJS