Dear Tarek,

you may want to have a look at ICH Q1E (see link), Chapter 2, which should answer your question. In short: 6 M accelerated data (not only impurities) will define how far you can extrapolate from real time data when proposing shelf life.

In Addition: Assay and degradants should fit about together - e.g. if you have 5 % loss in Assay but impurities remain 0.0 %, you may want to have a deeper look into your method's performance and understand the chemistry of degradation of the API better!

Best regards

Holger

http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1E/Step4/Q1E_Guideline.pdf

According to EU pharmacopoeia, my formulation specs are:

API within 5% from labeled content and no secondary peak (degradation product) to be more than (0.2%). If the increase in degradation product concn. should increase in line with the decrease in API, then shelf life will be very limited; unless that degradation product is not stable enough to keep accumulating.

Results of degradation- and related-product assays are reported as is the result for the active drug ingredient, bearing in mind the specifications established for the active drug (with degradation- and related-products limits).  The increase in degradation products should correspond with the decrease in active drug:  if it doesn't, as stated above, look again at the validation of your stability-indicating assay method.

The degradation products and impurities assay(s) aren't typically used to estimate the pharmaceutical product shelflife...just the API.  But the degradation and impurities are important in the risk assessment of safety of the API and are assessed over the shelf life of the product.  Most jurisdictions have set some threshold limits for degradants/impurities on the basis that very low levels are unlikely to be harmful.  If your degradants/impurities are well characterised and have known toxicity profiles then an argument can be made to what allowable limits should be (provided the API remains within the prescribed assay limits)..likewise a degradant/impurity could render the pharmaceutical unsaleable if it reaches a toxic level prior to the API falling outside specified limits.