Bioequivalence and Bioavailability Forum

Dear Thangairulappan S,

❝ 1) Why we are fixing IS variation range ±50% from the average IS response of accepted CCs &

❝ QCs.

Your choice. Guidelines say you should monitor IS response, but do not specify how. Bear in mind that ±x% limits are useful, but not sufficient. Tons of reasons why in this issue of Bioanalysis.

❝ (while using a deuterated IS why we not keeping ±15% or ±20% or some other range).

Actually, a number of labs are pleading that you could use wider acceptance limits if using a stable isotope labelled IS. The tighter the limits you set, the higher the number of samples you will have to re-analyse because of IS variation, with little or no added value.

❝ 2) If in one project ISR failure observed frequently/continuously means what will go to next

❝ actions and please give some examples with clarification for the reasons for those

❝ failures.

Some good reading material:

Aimin Tan, Sofi Gagnon-Carignan, Sylvain Lachance et al.
Beyond successful ISR: case-by-case investigations for unmatched reassay results when ISR passed
Bioanalysis (2011) 3(9), 1031–1038

Manish Yadav, Pranav S Shrivastav
Incurred sample reanalysis (ISR): a decisive tool in bioanalytical research
Bioanalysis (2011) 3(9), 1007–1024

Some interesting information also in this more recent paper. However I would not follow all of their proposals and recommendations, as they may not be accepted by regulators:

Morten Anders Kall, Marco Michi, Barry van der Strate et al.
Incurred sample reproducibility: 10 years of experiences: views and recommendations from the European Bioanalysis Forum
Bioanalysis (2018) 10(21), 1723–1732