Hello folks.

I have a validated HPLC method for our drug substance (a peptide). Peak purity has been performed by LC-MS to confirm nothing is buried under the main peak. Forced degradation has been performed. Several process impurities have been identified. Drug substance is stable through 24 months at its recommended storage condition. There is only one impurity which increases on accelerated stability and it too has been identified (n-terminal acetylated form of peptide).

I am planning drug product method validation. I am using the same method for drug product as is used for drug substance. The drug product is a liquid solution administered by IV. The drug product formulation is very simple - drug substance + mannitol + water. As with drug substance, drug product is stable through 24 months at its recommended storage conditions. As with drug substance, there is only one impurity which increases on accelerated stability and it's the same one as seen in drug substance.

ICH Q2(R1) describes demonstrating specificity when the impurities are known and when they are not known.

In your opinion, should I demonstrate specificity by simply injecting the impurities into the drug product (and/or placebo) to show we don't have co-elution? Or should I perform forced degradation to ensure nothing could arise from an interaction with the mannitol?

I've searched these forums about my question and found this thread which is ten years old. Looking to see if there are updated opinions now.

http://www.chromforum.org/viewtopic.php?f=1&t=3960&hilit=forced+degradation+drug+product