Chromatography Forum

Hello All,
I got a strange situation with my method, which was originally validated and submitted to regulatory. Now with the same method samples are assaying about 95% and I need to increase 5% of the organic content of the sample diluent to get 100% assay.
Do I need to do full validation for this change? where can I find the guidance related to this? Please advise if you know. Thanks.

The general rule is that modifications to a method require full revalidation. Certain de facto adjustments are permitted by ORA Lab 5.4.5, but changes to sample prep are not included. Bottom line: yes, you have to validate the modified method (sorry!).

Thanks Tom,
this change what I suggested does not fall under the scope of ORA 5.4.5, do you think I still need to do full validation.

Yes, that's the whole point. Changes within the scope of ORA Lab 5.4.5 are "adjustments" and do not require revalidation so long as you meet system suitability. Anything else is a "modification" and *does* require revalidation.