Residual Solvents Control Checklist (ICH Q3C)

Solvent Inventory and Classification

Catalog and classify every solvent used.

• Are all solvents used in the synthesis and manufacture of the drug substance and product inventoried, including those used by suppliers? *
• Is each solvent classified as Class 1 (avoid), Class 2 (limit), or Class 3 (low toxicity)? *
• Are Class 1 solvents (e.g., benzene, carbon tetrachloride) eliminated or specifically justified and controlled? *
• Are solvents with no adequate toxicological data identified and justified?

Limits and Calculation

• Are Class 2 solvents controlled to the PDE using Option 1 (concentration limit) or Option 2 (dose-based)? *
• Are Class 3 solvents limited to 0.5% (5000 ppm) unless a higher amount is justified? *
• Record the calculated total residual solvent limit for the finished product (ppm).

Analytical Testing

• Is residual solvent testing performed by a validated gas chromatography method? *
• Is testing applied to the drug substance, excipients, or product where solvents are used or carried over? *
• Is a control-threshold approach used to justify reduced routine testing where levels are consistently low?

Documentation and Change Control

• Are residual solvent specifications approved by the quality unit and included in the release specification? *
• Is the solvent risk assessment updated when process routes or suppliers change? *