In September 2013, the Elemental Impurities Expert Panel reviewed the Step 2 limits of the International Conference on Harmonization (ICH) Q3D Elemental Impurities Working Group, which were released in June 2013 and recommended revisions to General Chapter <232> Elemental Impurities—Limits to partially align with the ICH Q3D limits. In October 2013, the General Chapters—Chemical Analysis Expert Committee endorsed the Expert Panel's recommendations.
On December 27, 2013 the USP announced the approval of General Notices section 5.60.30 Elemental Impurities in USP Drug Products and Dietary Supplements with an official date of December 1, 2015. Section 5.60.3 of the General Notices will make applicable General Chapters <232> Elemental Impurities—Limits and <2232> Elemental Contaminants in Dietary Supplements as of that date, which reflects a delayed official date approved by the Council of Experts Executive Committee to allow industry more time to implement the standard and is based in part on consultations with the Elemental Impurities Advisory Group. The implementation of General Chapters <232> and <2332> will also include removal of all references to General Chapter <231> Heavy Metals from monographs and general chapters in the USP-NF. The omission of <231> is scheduled to align with the date of applicability of <232> and <2232>, which will be published in Supplement 2 to USP 38—NF 33 with an official date of December 1, 2015.
In addition, USP is posting proposed revisions to General Chapters <232> and <233> Elemental Impurities—Procedures, which will be published for public comment in Pharmacopeial Forum 40(2) with a comment deadline of May 31, 2014. The revisions to <232> convey USP’s review of and subsequent partial alignment with the International Conference on Harmonization (ICH) Q3D Step 2 limits. USP’s proposed limits reflect a review of published toxicological data and studies, as well as expert review by toxicologists serving on the Elemental Impurities Expert Panel. In some cases, USP’s proposed limits diverge from the Q3D Step 2 limits, and USP has notified ICH of these divergences via a comment letter on the Q3D Step 2 document. In addition to the changes to the limits, the panel also recommended minor editorial changes.
A revised implementation timeline has also been published. In addition, a revised General Notice section and a letter that USP sent to John Kauffman at FDA on December 20, 2013 with USP's comments on the Step 2 ICH Q3D guideline for consideration by the Expert Working Group when moving the guideline to Step 4 is also available.