Perspective Gagnon-Carignan, Lachance, Saint-Laurent, Gendron & Lévesque
In-house ISR data available for the same assay/species?
No
Yes
In-house ISR data available for the same assay but different calibration range?
Provide a summary of ISR results (e.g. overall reproducibility rate)
No
Yes
Provide a summary of ISR results
In-house ISR data available for the same drug and samples collection procedure/matrix but different analysis conditions?
No
Yes
The justification will have to rely on the other response elements
Provide a summary of ISR results to show that there is no back conversion or stability issue with the collection/storage conditions
Figure 1. In-house incurred sample reanalysis data evaluation tree. ISR: Incurred sample reanalysis.
Finally, repeats from rejected runs could also sup-
port the analysis of the assay reproducibility. An ana- lytical run can be rejected for various reasons, for example, too many calibrators or quality controls out- side of the acceptance criteria, poor chromatography, a documented technical error, etc. Depending on the reason for the rejection, the results of some rejected runs can be compared with the repeat results to give some insight into the reproducibility of the method. For example, a run may be rejected because of qual- ity controls (QCs) that were switched by error during the analysis process. In principle, this error does not affect the quantitation of the study samples as they are back-calculated against the calibration curve and not the QCs. In such a case, it might therefore be per- tinent to run the reproducibility formula against the
224 Bioanalysis (2015) 7(2)
second analysis. As mentioned above, it is advisable to explain in the justification, why these runs are con- sidered as an adequate support to show the method reproducibility.
Nonanalytical repeats We call ‘non-analytical repeats’ the samples for which the result of the initial analysis, although analytically valid, is to be confirmed by another analysis because of a doubt on its exactitude, for example, investigational repeats and PK repeats. Nowadays, as
they are not permitted by several
regulatory agencies, less and less laboratories perform reanalysis based on PK reasons. However, they may be present in the less recent studies in which the lack of ISRs must be justified. Investigational repeats are
future science group
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