Chapter 20 - Extractables and leachables

Abstract

Leachables from drug product container closure system from primary and secondary packaging components that migrate into the drug product can have a potentially negative impact on patient safety. Analytical methods are needed to detect leachables in the drug product. The first step toward developing analytical methods for leachables is to identify the extractables that could become leachables by doing extraction studies. Extraction studies are designed to simulate both intended use and worst-case scenario models to identify the leachables that could potentially migrate into the drug product. Analytical methods are then developed with the sensitivity necessary to detect the potential leachables in the drug product at levels determined by the toxicity thresholds of the leachables. Analytical methods for leachables are validated in a way similar to methods intended to evaluate the stability of the drug product. Leachable analysis can then be used in the long-term stability studies or in migration studies designed to evaluate specific leachables.