Is there an expectation/requirement to initiate an OOS investigation for historical results on stability when impurity specification limits are tightened mid-study? Specification change is being made per FDA comment. Does it matter if the impacted results are for the RT vs ACC condition? If there is a requirement, reference would be appreciated!
I’m not an expert in this area, but in a lot of years of experience, I’ve not encountered a situation where tightening specs translated into an OOS scenario. Good justification and documentation in close coordination with QA and Regulatory colleagues (with equal application to RT and ACC conditions) should keep you in good standing with our friends at FDA. Comments by others with more experience in this situation are welcome.
I have encountered OOS when tightening of specs during mid-study. Before the change is implemented, we will evaluate if our product is able to meet the new specs. If the product cannot meet the specs, we do not implement the change immediately but will investigate the possible root cause. Two possible outcome that commonly arise from the investigation (based on our experience) in order to meet the new specs:
a) reduce product shelf life or
b) change the storage condition
However, we do not export our products to USA. It would be interesting to hear how your organization address the issue.