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I want to know different guideline applicable for incurred sample
reanalysis as I have gone through AAPS journal FDA recommendation
but I am not getting the clear cut acceptance criteria for accepting
incurred sample reanalysis and what to do if incurred sample
reanalysis fails to meets the criteria.
I also would like to know guideline for reanalysis of subject
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As you have mentioned Incurred sample reanalysis is just a
arecommendation and as of today there are no concrete guidelines laid
down by FDA as to how it needs to be approached. But all the
regulatory body wants to see is that you atleast start of in this
direction rather than do nothing. As far as laying down acceptance
criteria for the same is concerned, at the current moment it relies on
what you feel is most appropriate. In the event that the results still
do not comply with the laid down guidelines, you will have to make an
investigation for the same based on conditions like if you see a
prominent negative bias in all the Incurred sample tested, etc.
Accutest Research Laboratories.
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The following message was posted to: PharmPK
Hello mukul lakhani,
Incurred sample reanalysis will be assessed in all studies where PK
parameter serves as a primary endpoint. Reanalysis of incurred samples
refers to the reanalysis of a randomly selected portion of the study
samples to determine whether the original analytical results are
reproducible. Incurred samples reanalysis serves as an additional QC
measure for establishing the robustness of the bioanalytical method.
This reanalysis shall be performed on following type of studies
* Bioequivalence studies.
* Healthy subject population studies.
* Patient population & special population studies (Renally impaired
* Preclinical toxicology studies.
* Studies on combination dosing regimens.
Categorise the nature of study on above classification and the
acceptance criteria may vary and it is study specific.
* Reassay of the incurred samples will reveal issues related to the
* Compare the values of repeated or reanalyzed incurred samples with
the initial values (normal or original values) of a particular bio
* Fix a minimal % difference (in +/- values) between repeated
incurred samples & initial values of study samples. The average of the
above two values should be taken into account for calculation.
* It was suggested that 2/3 of the samples be within 20% of the
initial values for small molecules and 30% for large molecules. The
criteria should be stated in the SOP, and must be scientifically
* Results of assay reproducibility evaluation may be reported as
addendum to the method validation report. This could serve as a
reference for future studies.
* If incurred sample reanalysis expt has failed, perform
bioanalytical investigation & identify the root cause for failure. The
result should be evaluated in context of intended pre-clinical or
clinical outcome of the study.
Additional information on incurred sample reanalysis
Pls Refer to calibration & validation group (Canadian workshop report)
on incurred sample reanalysis provided in web site
Health Canada (TPD/HPFB) guidelines on BA & BE studies for incurred
sample reanalysis (http://www.hc-sc.gc.ca/).
Hope these inputs may help.
[Note two multi-line urls should be one line only - db]
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