• Q3A - Q3D Impurities

    Code Document Title Previously coded
    • Description :

      The core tripartite harmonised ICH Guideline was finalised under Step 4 in July 1997. This recommends the use of less toxic solvents in the manufacture of drug substances and dosage forms, and sets pharmaceutical limits for residual solvents (organic volatile impurities) in drug products.

      Maintenance Process

      A Maintenance process has been done to revise Permitted Daily Exposure (PDE), as new toxicological data for solvents become available. 

      Limit values for three residual solvents in drug products were revised on basis of the newly recognised toxicity data; lower PDE for N-Methylpyrrolidone being kept in Class 2 (limited by health-basis) and for Tetrahydrofuran and Cumene being placed into Class 2 from Class 3 (no health-based).

      Both revisions (PDE for THF and PDE for NMP) reached Step 4 of the process in September 2002. A corrigendum to calculation formula for NMP was subsequently approved on 28 October 2002. As per the new coding rule, they were incorporated into the core Guideline in November 2005.

      In February 2009, Table 2, Table 3 and Appendix 1 of the Core Guideline were updated to reflect the revision of the PDEs for N-Methylpyrrolidone and Tetrahydrofuran (Q3C(R4)).

      In October 2016, the PDE for Methyl isobutyl ketone (MIBK) was revised, and Triethylamine (TEA) was added as a news solvent. Based on new data, MIBK was moved from Class 3 (solvents with low toxic potential) to Class 2 (solvents to be limited). The new solvent Triethylamine was included in Class 3 (solvents with low toxic potential) (Q3C(R6)).

      In October 2018, the MC approved the error correction of the Permitted Daily Exposure (PDE) for ethyleneglycol (Q3C(R7)). Additionally, the MC approved the publication of Support Documents 1, 2 and 3, which include the summaries of the toxicity data from which PDEs were derived.

      Implementation :

      Q3C(R6) Step 5

      :

      EC, EuropeAdopted by CHMP, 15 December 2016, issued as EMA/CHMP/ICH/82260/2006

      FDA, US - Published in the Federal Register as of 7/25/17 Vol. 82 No. 141 pp. 34537-34538

      Health Canada, Canada - To be notified

      MHLW/PMDA, Japan To be notified

      Swissmedic, Switzerland - Refer to the press release on Swissmedic, Switzerland's website

      Implementation :

      Q3C(R7) Step 5

      Ongoing