Bioequivalence and Bioavailability Forum

Hello Farmacevt,

❝ Please advise what if the Lower limit of quantification for some of the subjects in the BE study is greater than 5% of Cmax (not for the pre-dose concentrations).

There should be a rule about it in your SOPs or in your protocol. Perhaps you are asking because that isn't the case?

For EU: My experience is that it happens now and then and some assessors are very vigilant about it, while others don't give two tiny mouse droppings.
At one extreme you may need to eliminate those subject periods that are affected, which may mean a complete loss of a subject for stats if this is a 222BE design, since only subjects who contribute with T and R should be in the stats analysis.
At the other extreme, no need for any action. You may land anywhere in between the two. It depends and it does not only depend on the RMS but also the actual assessor within the agency at the RMS.

If you have many such cases you can get flagged for inspection. It would be tremendously bad planning if your study is deemed futile due to this matter.

If you want a smooth process, don't submit with NL or DE as RMS. Submit in SE or DK or AT, if you can get a slot.