The technical challenges associated executing a strategy to address the toxicological risk associated with patient exposure to leachables vary depending on the unique characteristics of the dosage form. For Metered Dose Inhalers (MDIs), widely regarded as the highest risk dosage form from an E&L perspective, often contain leachables at levels that require a strategy to be put in place to control leachables in commercial batches of the drug product after approval. Topical drugs have complex formulations that present unique analytical challenges to analyze the topical drug product and/or justify an appropriate surrogate solvent system to generate extracts of the container closure system. Large Volume Parenteral (LVP) drug products are similar to Small Volume Parenteral (SVP) drug products in the sense that most are aqueous based, however the increased daily dosage volume present analytical challenges that are pushing the boundaries of science and the capabilities of the state of the art analytical instruments that are available today. The talk discusses some of the complexity associated with deriving the Maximum Daily Dosage (MDDs) of LVP drug products and how this can impact the AET. Furthermore, the challenges associated with detecting and identifying extractables/leachables in line with evolving Safety Concern Thresholds (SCTs) is discussed along with when it is appropriate to consider the value of incorporating risk based concepts into a leachable study to ensure the level of effort (i.e. extent of testing) is commensurate with the level of risk.

This presentation was recorded on March 24 and is part of a series.