Chromatography Forum

We recently had some routine HPLC stability work performed by a CTL. They notified us when the assay method was run using the wrong injection volume; the method was validated using an injection volume of 5-µL and the method was run using 10-µL.

Powers above me are saying that the data can be saved IF, to support the increased injection volume they would like the CTL to include the calibration parameters for their HPLC, specifically the injection loop. If the increased volume still falls within their calibration parameters, that coupled with the standards being injected at the same level and passing system suitability, the validity of the run can be supported.

I assumed this was a cut and dry issue... if the wrong injection volume is used, the data is invalidated with a very clear assignable cause. The samples and standards are injected again using the proper injection volume. Is this not the case?

I am quite agreed with you, MatthewG. If the method was validated, in order for the data to also be valid, the method must be executed under the same conditions as it was validated.

[/assumptions: we're talking Pharma, finished forms, QC setting]
If -
1) the LC's calibration records indicate that the 20µ volume is within the range tested for that particular LC and
2) the volume injected does not result in the total amount of API injected falling outside the method's validated range (typically 80% of lowest dosage unit to 120% of highest dosage unit for multiple strengths of a given API), you *may* be able to get away with it, provided nobody has an SOP saying that such exceptions are forbidden.

That said, the above is from a RA point of view. Legally, the CTL screwed up and is probably obligated by the terms of the contract to rerun those samples at no additional charge. If not, you need a new contract writer and/or new counsel. This all assumes, of course, that your management is not in a big damned hurry to have the numbers (and we all know how often that this is the case).

Any chance that the robustness in the original validation included doubling the injection volume ? Probably not, but it might be worth checking the paperwork.

Peter

What is a CTL? Cat tongue lick? Conniving Tweaker Lobbyist?

Clear cut human error method deviation by the lab in question. Where the parameter used (injection volume in this case) exceeds that of the method validation robustness design space invalidate the original run and repeat. Any justification for keeping the analysis in this case would be extremely difficult to make strong enough to stand up to regulatory scrutiny.

The question that would be raised from a deviation point of view is why was their system suitability not evaluated prior to analysing the samples. That would be the only ? for me as this could have avoided a deviation and prevented the delay in you getting your data.