Regulatory Focus™ > News Articles > 2019 > 8 > USP Consults on Impurity Reporting Threshold Changes

USP Consults on Impurity Reporting Threshold Changes

Posted 19 August 2019 | By Michael Mezher 

USP Consults on Impurity Reporting Threshold Changes

The United States Pharmacopeia and National Formulary (USP-NF) last week launched a three-month public consultation on a proposal to change how impurity reporting thresholds for drug product and drug substance monographs are handled.
 
“As part of our commitment to ongoing monograph modernization, USP is updating organic impurities testing for articles subject to USP-NF standards,” USP writes, noting that its current approach relies on International Council for Harmonization (ICH) Q3A/B-based limits for detecting and reporting impurities.
 
According to USP, in 2016 the US Food and Drug Administration (FDA) requested that impurities reporting thresholds be left out of drug product monographs out of concern that including reporting thresholds in the monographs could lead to non-specified toxic impurities not being identified or reported.
 
“FDA commented that reporting thresholds for drug products vary based on product-specific factors and should be addressed as an application assessment issue,” USP writes, noting that FDA uses ICH reporting thresholds as guidelines, but deviates from them in certain instances.
 
USP says that FDA recently notified it that the agency holds the same concerns regarding reporting thresholds for drug substance monographs. As a result of FDA’s concerns, USP is proposing to remove reporting thresholds from its proposed monographs and stop including them in new monographs going forward.
 
Specifically, USP is proposing to give its expert committees the option of deleting proposed reporting thresholds from proposed monographs without republishing the proposed monographs in the Pharmacopeial Forum (PF). USP would also stop including reporting thresholds in future PF proposals for drug substance and drug product monographs.
 
Additionally, USP says it “will continue including a sensitivity solution and signal-to-noise requirement in monographs, to ensure that the sensitivity of the equipment is sufficient to reliably integrate any impurities that are included for calculating the total impurities result.”
 
For existing monographs, USP says it will not remove reporting thresholds until the monographs are revised for other reasons.
 
USP says the proposed policy change would affect 73 drug product monographs and 13 drug substance monographs.
 
USP

Regulatory Focus newsletters

All the biggest regulatory news and happenings.

Subscribe