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Updated: Mar 2, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Topical otic drugs in a multi-purpose manufacturing facility: a guide on determination and application of permitted
Lisa Wiesner1, Maarten Prause1, Ester Lovsin Barle1
1a Novartis Pharma AG, Postfach , Basel , Switzerland.
Abstract:
Due to newly introduced EU GMP (Good Manufacturing Practice) guideline for Medicinal Products for Human and Veterinary use, product specific permitted daily exposure (PDE) for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. European Medicines Agency (EMA) guidance on setting PDE limits so far focused on systemic administration routes such as intravenous (IV), oral or inhalation. This article provides guidance on setting PDE values for risk management purposes in multi-purpose facilities for active pharmaceutical ingredients (APIs) applied as topical otic drugs to the outer ear canal. The therewith determined PDE otic, is used for the calculation of maximum safe carry-over (MSC) in manufacturing scenarios where a topical otic product is manufactured followed by another topical otic product.
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