Understand the difference between extractables and leachables, how they relate to materials, packaging, manufacturing systems and drug products, and why the distinction matters in ICH Q3E risk assessment.
Extractables are chemical entities that can be released from a material or component under controlled extraction conditions. Leachables are chemical entities that actually migrate into the drug product under the real or simulated conditions of manufacture, storage and use.
The distinction matters because an extractables study explores what a material or system could release, whereas a leachables study evaluates what reaches the drug product under the relevant product lifecycle conditions.
Where can E&L originate?
Potential sources include manufacturing equipment, process-contact materials, container-closure systems, packaging components, delivery devices and administration components. The relevance of each source depends on contact conditions, material composition, process conditions, formulation characteristics and patient exposure.
Why extractables data are useful
Extractables studies help characterize the chemical space associated with a material or component and can support material selection, supplier qualification, analytical target selection and the design of subsequent leachables studies.
Why leachables are the patient-safety focus
Leachables are directly relevant because they represent actual or plausible chemical exposure from the drug product. Their assessment therefore connects analytical data with toxicological qualification and patient exposure.
How ICH Q3E connects the two
The draft ICH Q3E guideline provides a holistic framework that combines risk assessment, materials and process understanding, analytical studies and safety assessment. Extractables and leachables are not isolated laboratory exercises; they are part of an integrated risk-management process.
Frequently asked questions
Are extractables and leachables the same thing?
No. Extractables are substances released under extraction conditions, while leachables are substances that migrate into the drug product under manufacturing, storage or use conditions.
Does every extractable become a leachable?
No. An extractable may never migrate into the drug product at a relevant level.
Why study extractables if leachables are the actual exposure concern?
Extractables data help characterize potential chemical sources, support analytical planning and inform which compounds may require monitoring in leachables studies.
Can E&L come from manufacturing equipment as well as packaging?
Yes. Manufacturing components and systems, packaging, delivery devices and administration components can all be relevant sources depending on the product and process.
Is ICH Q3E final?
No. As of October 2026, ICH Q3E remains a draft guideline and the public consultation has closed.
