Total Impurities (% area/area) Specification Setting

[Rob Burgess]

Hi All,

The ICH does a fairly good job of letting you know how to set spec. limits for individual impurities.

However, it doen't appear to mention what to do with your total impurity count i.e. addition of all impurities over your reporting threshold.

Is there any official regulatory guidance? We have some internal guidance that mentions 4.0% total impurities but I don't know how this figure was justified to be honest. Any ideas?

[Alex Buske]

Hi rob,

As far as I know there is no guidance or something on the sum of impurities.

Alex

[krickos]

Hi

Can not recall any directly either, there are some special type of drug substances and drug products, source etc that could be the reason but to generalize or a common case for drug substances:

Residual solvents. Not more than 0,5% in total, that I think is actually mentioned unless somehow motivated.

Organic impurities: Not more than 0,5% is prefered, most newer monographs leans in this direction.

But as I said seems a bit from case to case, depending on source, manufacturing possibilities, use (?) etc.