USP <467> - Residual Solvents

What it says

General Chapter <467> describes analytical procedures, typically gas chromatography, for identifying and quantifying residual solvents in drug substances and products, applying the same three-class toxicological categorisation and permitted daily exposure limits described in ICH Q3C(R9).

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

What it means in practice

• This chapter provides the specific USP analytical testing methodology that operationalises the ICH Q3C(R9) residual solvent classification and limit framework, similar to how <232>/<233> operationalise ICH Q3D(R2) for elemental impurities.
• Method validation for residual solvent testing must demonstrate adequate sensitivity for each solvent class, since Class 1 solvents carry much stricter limits requiring correspondingly more sensitive detection.
• Selection of which solvents to actually test for should be based on a documented assessment of which solvents are genuinely used or could reasonably be present in the specific manufacturing process, not a generic, undifferentiated panel.

What inspectors look for

• Whether residual solvent testing panels are based on a documented assessment of solvents actually used or plausible in the specific manufacturing process.
• Whether analytical method validation demonstrates adequate sensitivity relative to the applicable permitted daily exposure limit for each tested solvent.
• Whether a process change introducing a new solvent triggers reassessment of the residual solvent testing and control strategy.

Related regulations