ICH Reverts to Previous Version of Guideline on Residual Solvents
The International Council for Harmonisation (ICH) has further explained why it decided to go back and change the Permissible Daily Exposure (PDE) for ethylene glycol (EG), and then more recently, to reverse that decision and revert back to the original figure.Prior to 2017, the ICH Q3C guideline, which deals with residual solvents, included a Summary Table 2 that listed EG as a Class 2 residual solvent with a PDE of 6.2 mg/day. But in 2017, ICH was notified by an external party of a discrepancy between Summary Table 2 and the monograph for EG listed in Appendix 5, which indicated that the PDE was 3.1 mg/day.
“This issue was presented to the Q3C EWG [expert working group] for discussion and given the lack of any additional information or awareness of a supporting rationale for the value listed in Summary Table 2, the EWG considered the discrepancy to be a transcription error in the Summary Table 2. The EWG then recommended that Summary Table 2 be revised to reflect the PDE indicated in the Appendix 5 monograph (3.1 mg/day),” ICH explains in a statement from July.
The error correction was finalized in 2018, but this year, ICH says it received a request to suspend the error correction.
“Based on archival documents and a review of the literature, it appears that the EG PDE of 6.2 mg/day was accepted at Step 4 of the Q3C guideline in 1997 following reassessment of the toxicity data. However, while Summary Table 2 was revised to reflect the updated PDE, the Appendix 5 monograph was not. This information was evaluated by the EWG and the group concluded that the original PDE value listed in Summary Table 2 (6.2 mg/day; 620 ppm) was appropriate and recommended reinstituting the PDE value for EG. Therefore, Summary Table 2 has been corrected to reflect a PDE of 6.2 mg/day and 620 ppm,” ICH adds.
Moving forward, officials said at a meeting in April that the Q3C(R8) guideline will develop PDE levels for three solvents: 2-methyltetrahydrofuran, cyclopentylmethylether and tert-butanol. A draft guideline is expected by the end of 2019.
Reinstatement of ICH Q3C(R6) Guideline available now on the ICH website