Step 2b draft Q3C(R8): Impurities: Guideline for Residual solvents – Released for public consultation

Step 2b draft Q3C(R8): Impurities: Guideline for Residual solvents – Released for public consultation

Published on: 6 Jul 2020

The ICH Q3C core guideline was finalized under Step 4 in July 1997, providing recommendations on the use of less toxic solvents in the manufacture of drug substances and dosage forms, and setting pharmaceutical limits for residual solvents (organic volatile impurities) in drug products. In 1999, a Maintenance Expert Working Group (EWG) for the Q3C Guideline was setup to enable the revision and inclusion of new Permitted Daily Exposure (PDE) levels as new toxicological data for solvents become available.

As part of the Maintenance Process, the Q3C(R8) Maintenance EWG has been working on the PDE levels for 2-methyltetrahydrofuran (2-MTHF), cyclopentylmethylether (CPME) and tertiary-butyl alcohol (TBA) with the objective to add these new solvents to the guideline. This 8th revision of the document was endorsed by the Members of the ICH Assembly under Step 2 on March 25, 2020.  The draft Q3C(R8) document contains only the PDE levels for three solvents: 2-MTHF, CPME and TBA that were agreed to be included in the revision. Further to reaching Step 4, these PDEs would be integrated into a complete Q3C(R8) Guideline document.

The draft Q3C(R8) document includes toxicological data and proposed PDE for 2-MTHF, CPME and TBA. Based on EWG’s review of available toxicity data, CPME and TBA are placed into Class 2 “Solvents to Be Limited” and 2-MTHF is placed into Class 3 “Solvents with low toxic potential”.

In relation to this, on June 30, 2020, Heath Canada published a notification inviting comments on the draft guidance. All comments forwarded to Health Canada will be transmitted to the ICH as is, with the disclaimer that they are provided for information and do not necessarily represent the views of Health Canada, except as specifically indicated in separate comments.

As appropriate, organizations may alternatively wish to provide comments to affiliate association in the United States, Europe or Japan for their input directly to ICH.

Comments to Health Canada should be submitted by Friday July 31, 2020 in order to allow sufficient time for their assessment and subsequent transmission to the ICH.


1.       Release of draft (step 2) ICH guidance: Q3C(R8): Impurities: Residual solvents (dated Jun. 30, 2020) -

2.       Ongoing Public Consultations – Maintenance of the Guideline for Residual Solvents

Author:  Preetha Prabhu