USP <1663> and <1664> - Extractables and Leachables - Assessment Framework

What it says

Chapter <1663> addresses extractables assessment, laboratory studies under exaggerated conditions to identify substances a material could potentially release, while Chapter <1664> addresses leachables assessment, the study of substances actually migrating into a drug product under real storage conditions, together providing USP methodology closely aligned with the ICH Q3E framework.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• These two chapters divide the extractables and leachables assessment process the same way ICH Q3E conceptually frames it, extractables as the exaggerated-condition screening study and leachables as the real-condition confirmation study, providing specific USP methodological guidance implementing that same conceptual framework.
• Analytical method capability is central to both chapters, since extractables and leachables are often present at very low concentrations requiring highly sensitive, well-validated analytical methods to detect and quantify reliably.
• The relationship between an extractables study's findings and a leachables study's actual monitoring targets is a critical design link, since a leachables study that fails to monitor for substances the extractables study identified as plausible would leave a genuine control gap.

What inspectors look for

• Whether leachables monitoring targets genuinely reflect what the corresponding extractables study identified as plausible substances of concern.
• Whether analytical methods used for extractables and leachables testing have documented sensitivity and specificity adequate for the very low concentrations often relevant to this testing.
• Whether extractables and leachables assessment is revisited when packaging materials or manufacturing process contact materials change.

Related regulations