USP monograph verification

[broncos]

Hi, All,

Who can tell me what kind of verification of USP monograph is required for a drug product (cream). Reading USP <1226> did not help.

1. If monograph is used as written:
Specificity - positively full forced degradation study is needed, but what else? What about accuracy and recovery? impurities accuracy and precision?

2. If no changes needed in the procedure to pass system suitability, but minor changes are made (described in the <621> as allowed) in order to improve chromatography, then is it still subject of verification or full validation? If two allowed changes made?...

Sorry for the confusion, usually we develop our own methods, so this is an exception.
Thanks!

[syx]

since the procedure is not modified, we perform specificity, accuracy, and precission tests. full forced degradation study could be performed to the placebos to ensure that there is no interference peaks in the retention peak of the main peak.

[danko]

Hi Broncos,

I’m not a pharmacopoeia expert, but I submitted a chromatographic method to USP recently and I was asked for a system suitability sample-preparation procedure along with acceptance criteria. And I think it’s only reasonable to include it the method description.
Now if the method you are planning to adopt includes the above mentioned attributes, I think you should prepare the system suitability sample (it could be temperature induced degradation, acidic treatment, UV-light treatment etc.) and demonstrate the same or better specificity (selectivity, resolution and quantitative consistency). Once you’ve done that you should demonstrate that the adopted method has the adequate accuracy (here you can use an USP reference material) and finally you should document the intermediate precision (6 different setups with at least 2 different columns, mobile phase preparations, HPLC systems, chromatographers - all statistically randomized).
If everything indicates equivalency, I see no reason for not accepting your adaptation as valid.

Best Regards