Maintenance Procedure for Q3C  
This Maintenance Procedure has been developed by the International Council for 
Harmonisation (ICH) for revising the existing ICH guidance for industry Q3C Impurities: Residual 
Solvents (ICH Q3C) to include new solvents and revising existing permitted daily exposures 
(PDEs) for solvents already listed in ICH Q3C as new toxicity data for solvents becomes 
available.  
Data and/or proposals pertaining to the revision of ICH Q3C with supporting information can be 
submitted directly to the ICH Secretariat at admin@ich.org.  Information provided within a 
proposal should be based on significant toxicity data from studies such as repeat-dose toxicity 
studies, reproductive toxicity studies, genotoxicity studies, carcinogenicity studies and/or other 
relevant studies.  Single-dose toxicity data alone are not sufficient.  The toxicity data should be 
of sufficient quality to calculate a PDE.   
The ICH Secretariat will share any proposals received with the Q3C Expert Working Group 
(EWG) Rapporteur and ICH Coordinators.  The Rapporteur will facilitate the review of any 
proposals received by the EWG, and the EWG will make a recommendation on whether the 
proposal should be supported by the ICH Management Committee (MC).  
If a proposal for maintenance is supported by the EWG, the ICH Secretariat will subsequently 
notify the ICH Coordinators and MC.  The MC will then provide a recommendation to the 
Assembly on whether the EWG should be tasked with making the revision.   
A revision will be considered only on presentation of new data or previously unrecognized 
toxicity data sufficient to result in a significant change, or because of convincing evidence that 
the existing data used to calculate a PDE are invalid.  Minor changes in a PDE will not be 
considered.  The Rapporteur, with the consensus of the EWG members, will assign data reviews 
to the EWG and request subsequent recommendations.  
Based on the discussion, with requests for further information to the proposing group and/or 
individual as appropriate, the Rapporteur will prepare an assessment report based on the 
EWGs approval with a recommendation to accept, with or without modifications, or reject any 
proposed revisions.   
After endorsement by the Assembly, either at the next formal meeting or by electronic 
endorsement, the recommendation of the EWG will be published in each region for public 
comment (Step 3 of the ICH process).  In addition, the proposal will be provided to each 
pharmacopoeia for their publication.   After closure of the public comment period, the Rapporteur may convene a meeting of the 
EWG or will rely on correspondence or teleconferencing to consider the comments and finalize 
the proposal for the revised ICH Q3C.  The final recommendation for ICH Q3C and 
implementation is then forwarded to the Assembly for adoption in consultation with the MC.  
Implementation will follow regional practices.  With approval of the ICH Assembly, the change 
will be provided to the pharmacopoeias at the regional/national level for publication.  
When a new or revised PDE is recommended by the EWG, approval by the ICH Assembly is 
required.  Once approval occurs, the information should be disseminated as quickly as possible 
to all ICH participants and other members of the chemical and pharmaceutical communities.  It 
is recommended that the following actions should be taken by the Assembly to ensure rapid 
transmission of the new information:  
  Publish relevant information on the ICH Web site  
  Request publication of revisions by the pharmacopoeias of the ICH regions in their 
Forums or web sites  
  Request  that  the  members publish the new or revised PDE information on their 
respective web sites