I have a situation where a nitrosamine is detected in finished drug product stability batches stored under accelerated (40°C/75%RH) and intermediate condition (30°C/75%RH), but consistently below the 10% of the AI at long term condition (25°C/65%RH), even at the end of shelf life. The long term is also the patient relevant condition in this case.
Since the results on the storage condition relevant for the patient are consistently below the 10% of the AI (even in batches at expiry), should I include the nitrosamine in the specification of the finished drug product based on the intermediate and accelerated conditions results?
I kindly would like to hear your experience in these cases. Thank you in advance.
I would suggest to rely in the commercialisation condition you have for your drug product. The accelerated and intermediate conditions data are mostly for example to give provisional shelf life while having your long-term stability data studies concluded.
Having said this, I infer your long term stability study is concluded, your leaflet do not say for example “Do not store at temparature higher than 30°C” meaning using climatic zone IV data and so on.
Finally, my reading is that the kinetics at Zone II are not meaningful enough to move over the activation energy of the reaction. Therefore, be careful to not introduce “more energy” into the process in the future, to avoid passing that threshold.
I partially agree with Diego. Accelerated data are used to determine storage conditions.
however it is not clear to me whether it is within specs for 4075. if it is >AI and then stb at 3075 has been placed, it is possible that Authorities request for storage conditions.
other than that, I agree that routine test should be concluded based on 2560 results.
As per our experience, accelerated data is merely to decide the extrapolation of the shelf life & to have the quick idea of the product behaviour. However, agency is more focussed on the impurity levels during the entire shelf life of the product. So if levels are <AI at recommended storage conditions, it should not be an issue to decide the Omit testing approach.