How exposure, route, duration, structural concern and toxicological evidence are integrated when contextualizing the level of concern for an NMI.
An impurity’s level of concern cannot be determined from structure alone. It depends on how the available hazard information relates to the magnitude and pattern of patient exposure.
Exposure
Daily amount, duration and route determine the practical relevance of a potential hazard.
Severity and plausibility
The nature of the suspected effect and the strength of the evidence matter.
Data quality
Robust experimental or clinical data carry different weight from uncertain model predictions.
Decision context
The assessment should explain whether the available evidence supports the proposed specification or whether additional work is needed.
Frequently asked questions
Is level of concern a single universal score?
No. It is a contextual scientific interpretation.
Does higher exposure always mean unacceptable risk?
No. It must be interpreted relative to the hazard evidence and applicable limits.
Why include route and duration?
They can materially change the biological relevance of exposure.
Can in silico results contribute?
Yes, as part of a broader weight of evidence.
