Bioequivalence and Bioavailability Forum

Hi Hiren!

❝ Vietnam follows ASEAN Guideline (which is in line to EU)

Not quite. Your quoted statement comes from the obsolete 2001 NfG. Since 2010 (the current BE GL) nonparametrics are

Taboo in the Eeh-Yooh.

❝ I am working on a combination tablet with one molecule for which Tmax is important while for other molecules there is no relavance of Tmax.

❝ 1. How to decide a clinically relevant range for Tmax?

Ask a specialist in the field for a justification.

❝ Should I upfront define it in Protocol?

Yes.

❝ What is the most appropiate literature for deciding the clinically relevant range?

Duno; ask the specialist from above. If everything is unclear either ask the agency or define an acceptance range based on the reference’s t_max. Note that you are working with untransformed data, so the conventional acceptance range is 80–120%* (±20%). If safety is not of concern the ASEAN GL allows prospectively widening the acceptance range for C_max to e.g. 75–133.33%. Following the same logic the AR for t_max would be 75–125% (±25%).

❝ 2. How to tackle such FDC products in context to above matter? Whether there will be two different clinically acceptable ranges for Tmax?

Theoretically yes. But didn’t you say in your case t_max of the second API is clinically not relevant?

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• Strictly speaking the acceptance range should also be defined in the linear scale.
  Example: t_max,R 2 h, AR of T–R ±0.4 h.