Chromatography Forum

Hi all

according to the PhEur and USP, certain mobile phase adjustments are allowed as long as they are within range and the system suitability criteria are met.

Does this apply only to methods listed in the monographs.?
or can it be applied to in-house validated methods, even if it wasn't covered in the robustness during the validation. ?

Hi all

according to the PhEur and USP, certain mobile phase adjustments are allowed as long as they are within range and the system suitability criteria are met.

Does this apply only to methods listed in the monographs.?
or can it be applied to in-house validated methods, even if it wasn't covered in the robustness during the validation. ?

I believe that those adjustments are intended for the PhEur and USP methods. But ORA allows similar changes for industry-developed methods, see page 14 of this https://www.fda.gov/downloads/ScienceRe ... 092147.pdf

And here's the Appendix https://www.fda.gov/downloads/ScienceRe ... 173090.pdf

I believe that ORA Lab 5.4.5 adjustment limits technically apply only to FDA labs running methods submitted by industry. I typically recommend to our consulting clients that they write an SOP on adjustment and simply copy ORA Lab 5.4.5

Yes, it's a nitpick, but thar way you're covered in case you encounter an over-zealous reviewer.

I believe that NO ONE actually KNOWS what would be OK to an FDA auditor, depends on auditor, auditor's mood, whether auditor is in your town visiting friends or relatives, etc.

A retired government GLP auditor tried explaining all this to us.

Anyway, my pointy-haired boss wouldn't allow ANY changes no matter waht <621> stated, but quoted the USP as gospel. Then I asked him what it meant in "Volumetric Solutions" to standardize NaOH "frequently", whether that was every hour, every day, every week, etc....he just got mad at me and said do what it says !

If I were you (ctec) I would make an adendum to the method validation exploring/documenting the pH effect on the separation and ultimately the results.
It (pH) clearly has an influence on the method performance since you need to adjust it to a certain value more precisely than originally assumed.
So, an auditor (FDA or whatever) will most probably focus on the validity of pH adjustments in case of he/she realizes that the validation does not include that part.

Best Regards