Bioequivalence and Bioavailability Forum

❝ First of all as per ICH "reanalysis of study samples for a PK reason (e.g., a sample concentration does not fit with the expected profile) is not acceptable, as it may bias the study result."

My favorite topic: In 2004 or so there was a round table discussion - "PK samples reanalysis - to do or not to do" a topic everyone want to talk but every one is afraid. The consensus was you can reanalyze PK samples if there is a compelling reason - sponsor or CRO MUST have an SOP before the analysis start. Another important point has been even though folks have SOP they don't enforce the SOP consistently across all subjects and all samples.

Sponsor perspective: CRO send garbage data and sometimes pulling down the study, when questioned on the quality response is so complicated citing several SOPs and guidances.

CRO perspective: Sponsor Cherry picks samples and ask for reanalysis our reputation may be at risk as we serve clients from different countries and we know global regulations, if an inspection occurs and 483 is issued our reputation is at risk.

Regulatory perspective: are these guys are covering up anything? - this is when the problem starts answer is full transparency - present all documentation submit your analysis both ways with original values and with reanalysis values.

As a sponsor if you are on an prestigious project or multiple projects you better have an well written SOP with a decision tree how you pick samples for reanalysis, how you pick PK repeats and who authorizes from the sponsor side, how you decide on reporting the sample concentrations after reanalysis. We had a criteria 1) pick one sample on either side of the suspected outlier, analyze each sample in duplicate 2) after reanalysis report 1) original value if the renalaysis value and original value don't differ no more than 15%, 2) report median or average value if the samples differ by 15-25%, 3) report suspected outlier as non reportable if the values differ by >25%.

Important points are 1) having an SOP before the study start 2) communicating that SOP with your CRO or BA lab, and 3) following the SOP consistently.

In your case sample switch happened, it is more a study compliance issue, you have to investigate root cause of sample switch suspicion, even if it is one or two samples if you can not assign a reason (usual case) it is only suspicion, then don't report the values (we have had an experience we suspected sample switch during pre-dose samples - as usual clinic said we are saints, CRO monitor said I did my job meticulously - a a sponsor we ended up losing 11 subjects and excluded that one entire center. but we presented the data with and without those subjects and it did not make any difference) moral of the story Full transparency - but sadly who pays for sloppiness of CRO or site staff?