ICH Q3E - Guideline for Extractables and Leachables

What it says

Extractables, substances that can be released from container closure systems, manufacturing equipment or packaging components under exaggerated conditions, and leachables, substances that actually migrate into the drug product under normal storage conditions, require risk-based assessment and control appropriate to the product's route of administration and the materials involved.

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

What it means in practice

• This is one of the newer ICH guidelines, harmonising a previously fragmented, largely region-specific and product-specific approach to extractables and leachables assessment into a more consistent global framework.
• Extractables studies, conducted under deliberately exaggerated conditions to identify the full universe of substances a material could potentially release, inform which specific substances leachables studies then need to actually monitor under real, normal storage conditions.
• Risk generally scales with route of administration, parenteral and inhaled products typically warranting more extensive extractables and leachables evaluation than oral solid dosage forms, given the more direct systemic exposure route bypassing normal barriers.

What inspectors look for

• Whether extractables and leachables risk assessment appropriately reflects the product's actual route of administration and the specific materials in its container closure system and manufacturing process contact surfaces.
• Whether a change to a packaging component or manufacturing material triggers reassessment of extractables and leachables risk.
• Whether leachables monitoring data is used to confirm extractables study predictions remain valid under actual product storage conditions over time.

Related regulations