Chromatography Forum

As an impurity does not grow over time during a stability study of a finished product. Can it be justified to test for this impurity at the begining of a stability study and not there after?! Are they specific guidelines i can reference for this?...Thanks for your help in advance

Hi

I Suggest you read up on the ICH Q3B (R) guideline, in section V there is an opening for exlusion of impurities.

Generally speaking ANY impurity occuring under the production or storage of the final product is listed under degradation products.
If the source of the impurity is related to the drug substance production (synthetic impurity) it is generally easier to exclude from the stability testing of the final product.

So read up on the guideline and put some effort into the justification of the specification.

I don't think you're gonna pull this one out
do you know where does this impurity come from? do you know what is it? can you show that there is no degradation pathway that can link API to this impurity?

The only difference between process impurities and degradation products is whether they appear and grow over time or are present at a pretty constant rate from the start of a study (or undergo secondary degradation and thus declining over time).

Your method and protocol should resolve and track each type of impurity.

Krickos is correct in that demonstrated process impurities (known synthetic intermediates, byproducts, starting materials) do tend to be left out of degradation profile descriptions because they are known to be at constant or falling levels. If one of these shows up at potentially toxic levels, the usual course of action is to address either purification or synthesis of the API itself (I'm assuming that we're talking about a finished pharmaceutical product here).