Chromatography Forum

When developing a generic drug product, if the generic version has an unknown impurity that it is also on the brand name product, is it ok to provide justification to avoid identifying the unknown based on the retention time being the same and the mass being the same? The values found in the generic product are lower than those observed in the brand name product but the identity of the peak is unknown , there is only matching retention times and mass. Any advice would be helpful, thanks.

It is ok to provide justification! When you follow the Monograph or the validated Methode from the original manufacturer don't Change anything, otherwise you must do a new Validation. Out of interest I would try to find out the impurities structure. Maybe later it is a good selling Point for your generic drug on the market.

Which levels of this unknown impurity are you seeing? If it's above the identification threshold defined by ICH Q3B, I'd suspect problems with authorities. Even if it's also in the originator.
If it's below the identification threshold, you're fine.

Values are above reporting threshold but are less than what the innovator has.

I'd say that for authorities it doesn't really matter what the originator looks like. If the unknown impurity is above the reporting threshold but below the identification threshold, you just have to report it as unknown impurity. If it's above the identification threshold, well, bad luck - you'd have to identify it...

I agree with HPLCaddict. However, you probably don't have to ID the compound if the unknown is observed in forced degradation/stressed samples but not in registration stability/release samples.......don't forget to check temperature excursion/shipping samples too. If you're seeing it above the ICH ID limit in your 6mths 40C/75%RH samples, you may want to "consider" ID the peak b/c it's likely to show up in your 24hrs stability samples at 25C/75%RH.....proactive approach! During product development, if the unknown impurity is exceeding the ICH qualification limit, you may want to ID the unknown peak, understand the degradation chemistry and optimize your formulation to mitigate this unknown. Ultimately develop a superior quality product......if you have the time!

Shadow, If the original manufacturer/developer hasn’t reported the impurity it’s in no way a justification of you not doing it either.
Your role is to document the quality of what you’re marketing and not what other manufacturers are marketing!

Best Regards