Extractables and Leachables Study Checklist

Study Scope and Design

Define materials and study conditions.

• Are all product-contact materials in scope identified, including primary packaging, filters, tubing, and single-use assemblies? *
• Is the study design based on a risk assessment considering dosage form, route of administration, and contact duration? *
• Are extraction solvents selected to bracket product properties (polarity, pH)? *
• Are exaggerated and simulation extraction conditions justified relative to actual use?

Analytical Evaluation

• Is an analytical evaluation threshold (AET) established and toxicologically justified? *
• Are orthogonal analytical techniques used (e.g., GC-MS, LC-MS, ICP-MS) to cover volatile, semi-volatile, non-volatile, and elemental species? *
• Are individual extractables identified and quantified above the AET? *

Leachables and Correlation

• Is a leachables study performed on actual drug product under real-time or accelerated stability conditions? *
• Is a correlation established between extractables and observed leachables? *
• Are leachables monitored over the product shelf life?

Toxicological Assessment and Control

• Is a toxicological risk assessment performed for identified leachables against safety concern thresholds? *
• Is genotoxic potential assessed for relevant leachables? *
• Is a control strategy documented and reviewed under change control for material or supplier changes? *