The impurity limit is in line with ICH Q3B. So why did the regulatory body still ask you to 𝑗𝑢𝑠𝑡𝑖𝑓𝑦 and 𝑡𝑖𝑔ℎ𝑡𝑒𝑛 𝑖𝑚𝑝𝑢𝑟𝑖𝑡𝑦 𝑙𝑖𝑚𝑖𝑡𝑠?
A very common reason is this:
The team sees impurity A, checks the ICH Q3B and says:
“𝘛𝘩𝘦 𝘲𝘶𝘢𝘭𝘪𝘧𝘪𝘤𝘢𝘵𝘪𝘰𝘯 𝘵𝘩𝘳𝘦𝘴𝘩𝘰𝘭𝘥 𝘪𝘴 0.5% - 𝘭𝘦𝘵’𝘴 𝘬𝘦𝘦𝘱 𝘵𝘩𝘦 𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤𝘢𝘵𝘪𝘰𝘯 𝘭𝘪𝘮𝘪𝘵 𝘧𝘰𝘳 𝘐𝘮𝘱𝘶𝘳𝘪𝘵𝘺 𝘢𝘵 𝘕𝘔𝘛 0.5%”
Sounds logical right?
But if the impurity routinely stays far below that level, the regulator may still ask:
“𝘞𝘩𝘺 𝘩𝘢𝘴 𝘴𝘶𝘤𝘩 𝘢 𝘸𝘪𝘥𝘦 𝘭𝘪𝘮𝘪𝘵 𝘣𝘦𝘦𝘯 𝘱𝘳𝘰𝘱𝘰𝘴𝘦𝘥?”
And that is when the team is left wondering:
“𝘉𝘶𝘵 𝘵𝘩𝘦 𝘭𝘪𝘮𝘪𝘵 𝘪𝘴 𝘪𝘯 𝘭𝘪𝘯𝘦 𝘸𝘪𝘵𝘩 𝘐𝘊𝘏 𝘘3𝘉 - 𝘴𝘰 𝘸𝘩𝘢𝘵’𝘴 𝘵𝘩𝘦 𝘱𝘳𝘰𝘣𝘭𝘦𝘮?”
The problem is this:
ICH Q3A and ICH Q3B thresholds are regulatory decision triggers. Thresholds that tell you when an impurity needs to be:
- Reported
- Identified
- Qualified
But that does not automatically justify the limit proposed in the specs. A threshold tells you 𝘸𝘩𝘦𝘯 the regulatory evaluation begins.
A specification limit still needs to be justified based on the actual impurity profile data. That’s why two submissions can both cite ICH Q3B and still receive very different regulatory outcomes.
So, if your team is still setting impurity limits by directly lifting identification or qualification thresholds from Q3B, this is your reminder:
Being ‘𝘪𝘯 𝘭𝘪𝘯𝘦’ with ICH Q3B is not the same as being suitable as a specification.
Read also: How to Set Impurity Limits in Drug Products
