Bioequivalence and Bioavailability Forum

Hi Achievwin,

I had the unpleasant experience of attending the “Chrystal City I” conference (Arlington 1990). For an early collection of publications see this post.
Quote from the 1991 paper:

Repeal Analysis – The protocol for repeat analysis should be established a priori. Some aberrant values may be identified which can be attributed to processing errors, equipment failure, poor chromatography or quality control samples outside predefined tolerance. Cautious use of ‘pharmacokinetic fit’ such as a double peak may call for repeat analysis of some samples in the study; but the reasoning should be clearly documented.

And from the one of 2000 – which lead to the FDA’s 2001 guidance:

Repeat Analysis: A standard operating procedure or guideline for repeat analysis and their acceptance criteria must be established a priori. This SOP or guideline should define acceptable reasons for repeating sample analysis, such as sample processing errors, equipment failure, poor chromatography, etc. Cautious use of “pharmacokinetic fit” such as double peak may call for repeat analysis of some samples in the study. The rationale for the repeat analysis and the reporting of the repeat analysis should be clearly documented.

The 2001 guidance:

Repeat Analysis: It is important to establish an SOP or guideline for repeat analysis and acceptance criteria. This SOP or guideline should explain the reasons for repeating sample analysis. Reasons for repeat analyses could include repeat analysis of clinical or preclinical samples for regulatory purposes, inconsistent replicate analysis, samples outside of the assay range, sample processing errors, equipment failure, poor chromatography, and inconsistent pharmacokinetic data. Reassays should be done in triplicate if sample volume allows. The rationale for the repeat analysis and the reporting of the repeat analysis should be clearly documented.

(my emphases)

In my CRO we had a blinded review of data by a pharmacokineticist (not the bioanalyst). We applied a similar procedure like you (until the EMA’s guideline was published in 2011). Only then we were protected against suspected sample mix-ups in the clinical phase (see this example, slides 9–11). History…

BTW, the ICH M10 guideline of 2022 (overruling the FDA’s and the EMA’s) allows reanalysis of pre-dose samples if their concentration ≥ LLOQ. Well, cough, why?