• 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)).

      The most recent maintenance of the Guideline, resulting in the current Q3C(R6) version, was to revise the PDE for Methyl isobutyl ketone (MIBK), and to add Triethylamine (TEA) as a new 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).

      Implementation :

      Step 5

      :

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

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      MHLW/PMDA, Japan To be notified

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

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      Health Canada, Canada - To be notified

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

      Q3C(R5) Revised PDE for Cumene (February 2011)

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CHMP, March 2011, issued as EMA/CHMP/ICH/82260/2006

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      MHLW/PMDA, Japan Adopted 21 February 2011, PFSB/ELD Notification No. 0221-1

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      FDA, US The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, 23 February 2012, Vol. 77, No. 36, p. 10754-5

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      Health Canada, Canada Implemented 29 January 2016 File #: 15-114085-837

      Q3C(R4)

      Implementation :

      Step 5

      EC :

      Adopted by CPMP, February 2009, issued as CPMP/ICH/28395

      Revised PDE for Tetrahydrofuran (September 2002)

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, September 2002, issued as CPMP/ICH/1940/00

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      MHLW/PMDA, Japan Adopted 25 December 2002, ELD Notification No. 1225006

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      FDA, US The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, Vol. 68, No. 219, p. 64352-64353, 13 November 2003

      Revised PDE for N-Methylpyrrolidone (September 2002) - View subsequent Correction

      Implementation :

      Step 5

      :

      EC, EuropeAdopted by CPMP, September 2002, issued as CPMP/ICH/1940/00

      :

      MHLW/PMDA, Japan Adopted 25 December 2002, ELD Notification No. 1225006

      :

      FDA, US The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, Vol. 68, No. 219, p. 64352-3, 13 November 2003

      :

      Health Canada, Canada -

      :

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