Chapter 13 - Extractables and leachables

Abstract

Leachables from sample container closure systems from primary and secondary packaging components that migrate into a drug products have a potentially negative impact on 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 as extractables the leachables that could migrate into the drug product. Analytical methods are then developed with the sensitivity to detect the leachables in the drug product at the threshold determined by the toxicity of the leachable. Analytical methods for leachables are validated in a way similar to the 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 specifically evaluate leachables.