validation question

[olivia]

Hi, I am validating a finished product method. The API only contains synthetic impurties which are controlled in the drug substance.

I have been given a protocol that states to perform accuracy at 80%, 100% and 120% for active assay which is ok.

But the protocol also asks for accuracy at lower levels by spiking placebo with drug substance at (0.1 %, 0.2 % and 0.5 %). I think this is wrong, since there are no degradants there should be no analysis at this level.

Can anyone confirm this for me please.

Thanks

Liv.

[krickos]

Hi

Not a pharma final product specialist but..

I can see that this makes sence unless you have a separate stability indicating method.

I belive this is pretty much expected, even if you would have forced degradation studies, normal/accelerated stability studies indicating no known degradation impurities, how would you in the future "prove" that changes made in production (final product, new excipient source, new packing or for example new API supplier etc) does not impact stability with a method that is not stability indicating?

Also for APIs we have to (ICH requirement) add a batch to the stability program each year, I would assume that goes for final products as well and if the method is not stability indicating then...??

[pkenny]

I agree with the protocol.

Don't confuse synthetic impurities in the API with degradants in the DP (or even impurities in the DP), they are different.

Synthetic Impurities in API - come from manufacturing process of API. Do not need to be measured in DP if they are controlled in the API.
Impurities in Drug Product - come from manufacturing process of DP. Need to be controlled in DP.
Degradants in Drug Product - come from degradation of DP during its shelf life. These need to be monitored during stability studies.

So even though you may only have synthetic impurities in the API to start with, there are several areas where you may see new peaks in the DP.

(Sorry if I read your original post incorrectly)