AI Limit for Topical Formulations (Ointments and Gel)

This may be a tricky question and generally regulatory bodies (e.g FDA/USP, EMA, etc) may have differing opinions when it comes to route- or site-of-action specific exposure to compounds of interest (either e.g leachables, impurities, degradants, etc.) and there applicable limits.

Just to highlight this, here the just recently FDA published draft guidance: " Quality Considerations for Topical Ophthalmic Drug Products, Oct 2023" (Quality Considerations for Topical Ophthalmic Drug Products | FDA). See Chapter IV for the FDA´s rationale “systemic vs ocular” effect.

But this is of course an “older discussion stemming from Genotox Impurities” which would also tangent the nitrosamines.