Bioequivalence and Bioavailability Forum

Dear All,

Recently we did a BE study and among dozens of analytical runs, there's a run where internal standard showed inconsistent response, as shown in the following figure.



I removed several double blank samples where IS responses are zero. Apart from that, all samples in the run are included, where unknown samples are from 3 subjects. IS responses of unknown and QC after around 100th injection start to climb upwards.

When asked why this run was accepted, the CRO said that the run fulfilled the criteria defined in their SOP so the run is acceptable and there is no need of repeat analysis.

Now, the product is shitty so we are far away from BE criteria. Therefore it really doesn't matter what are the true PK values for those subjects. Repeated or not, there is no way the study conclusion will be changed. New formulation will be developed.

However, from pure bioanalytical point of view, in my opinion, there's clearly something wrong here. If runs like this are deemed acceptable according to SOP and not even trig an investigation, I don't care what the creteria is, the SOP may need to be revised. At the least, the samples from 2nd half of the run should be repeated. I would repeat the whole run.

What's your opinion/experience on that? Any suggestions? Thanks.