Bioequivalence and Bioavailability Forum

Hello GM,

❝ As per the new Bioanalytical Method validation guidelines, "Study samples with concentrations listed below the LLOQ should be reported as below the LLOQ (BQL). Study samples with concentrations above the ULOQ should be diluted and re-analyzed, or the standard curve should be extended and revalidated."

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❝ This means, whether we have to replace BQL values with "zero" or can we keep as it is in the BE analysis without replacing those values with zero?

Those values are not measured as zero, they are BLLOQ or BQL or BLQ or whatever code you assign to them. However, it is a commonly accepted principle that when you do NCA on the series, you consider BLQ to be zero for the purpose of derivation of AUC. This works without problems generally, with a few exceptions; for example, there is no universal agreement on how to handle a BLQ between quantifiable concentrations after tmax when you do "linear up, log down". But I assure you there are very strong personal opinions

Your processes around sampling and reporting PK-data and doing NCA should be in an SOP, in my opinion.

❝ We have a situation that, one of our study is passing the BE with BQL values (without replacing those values with zero), but failed to attain the BE without BQL values(with replacing those values with zero).

Sounds like you are in a good position. But check what the software actually does with BLQs - at the end of the day this is what determines if the proof of BE is rigorous and scientific.