If an ICH Q3C class II solvent is used in the final step of a drug substance manufacturing process, the residual solvent limit in the drug substance specification should be set according to the ICH Q3C concentration limit for the class II solvent and routine analysis should be performed; If a class II solvent is used in earlier manufacturing steps, then routine analysis of the class II solvent may be waived by providing analysis results of suitable intermediates or final drug substance of six consecutive pilot scale batches or three consecutive industrial scale batches demonstrating that concentration of the class II solvent in the intermediates or final drug substance is less than 10% of ICH Q3C acceptable concentration limit for the class II solvent. Please refer to EU guidelines CPMP/QWP/450/03 -Rev.1 and EMEA/CVMP/511/03 -Rev.1 for further details.

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