Bioequivalence and Bioavailability Forum

Dear Rasha,

❝ Does that mean that carryover test must be done on daily bases before running study samples

I have an opinion and it is not a popular one from the perspective of labs.

I have debated it numerous times both private people and with regulators. My opinion is that even though a validation report always contains some carryover testing, and even though labs tend to state "we meet the highest standards" and "only the strictest compliance principles are followed" plus lots of other rubbish, chromatograms from studies in practice sometimes look very different from chromatograms from validations. Difficult questions about CO can be -and are sometimes- showstoppers.

For that reason I told sponsors that my preference is that they ask CROs to have at least one double blank immediately after the highest calibrator in PK runs and to handle it proactively if or when CO is seen. Handle it means doing something much better than just concluding it has no impact. Like disqualifying the run. In other words, taking it seriously, however inconvenient that is.
On one hand the CRO protests that since CO is tested at validation, there is no need to do this. I tend to respond that adding a single CO inj. in a run is neither a heavy expense nor an extra burden, and if the validation is representative of runs then there will not be trouble when they do it. I can't say this view is popular with labs. Most sponsors don't understand what I mean. Not because they are ignorant at all, but more likely because I have trouble explaining myself or explaining why the matter is important.

Along the same lines: When I grow up and get the supreme powers of a dictator and I will completely ban the nasty habit of debating carryover in the context of a predose sample right after the highest calibrator. Anyone violating this rule will be egged on the town square.