USP Announces Revision Timeline, Effective Date for Elemental Impurities Limits and Procedures

Jan 15, 2014
By PharmTech Editors

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 Dec. 1, 2015. This General Notices section will make applicable General Chapters <232>Elemental Impurities—Limits and <2232> Elemental Contaminants in Dietary Supplements as of that date.

The effective date 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, according to an update on the USP website.

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.

The revisions to <232> convey USP’s review of and subsequent partial alignment with the ICH Q3D Step 2 limits, USP reports. USP’s proposed limits reflect a review of published toxicological data and studies and expert review by toxicologists on the Elemental Impurities Expert Panel. In some cases, USP’s proposed limits diverge from the Q3D Step 2 limits, and USP reports it has notified ICH of these divergences. The panel also recommended minor editorial changes to both General Chapter <232> and General Chapter <233> Elemental Impurities—Procedures.

The revisions will be posted to USP’s website to allow for public comment on the proposed changes in advance of its publication in Pharmacopeial Forum 40(2).

The implementation of General Chapters <232> and <2332> also will 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 in Supplement 2 to USP 38—NF 33 with an official date of Dec. 1, 2015.

USP had specified the following revision timeline:
• Dec. 27, 2013: USP posts the final version of General Notices section 5.60.30, which includes the date of applicability of <232> and <2232>. USP also pre-publishes on the USP Elemental Impurities Key Issues web page the proposed revisions to <232> and <233>. 
• March 1, 2014: USP publishes the proposed revisions to <232> and <233> in PF 40(2) [March-April 2014] for public comment. Comments will be accepted only on the proposed revisions to the general chapters. 
• May 31, 2014: The 90-day comment period ends (comment period is from March 1, 2014 through May 31, 2014). 
• May 2014: The General Chapters—Chemical Analysis Expert Committee ballots on the removal of General Chapter <231> Heavy Metals. Note that the removal of <231> was previously proposed in PF 39(1) [January-February 2013] and will specify an official date that aligns with the applicability of General Chapters <232> and <2232>, which is specified in General Notices section 5.60.30 as December 1, 2015. 
• June 2014: The Expert Panel considers comments received on the proposed revisions and also reviews ICH Q3D Step 4 limits, which are expected in June 2014. The revised General Notices appears in the Second Supplement to USP 37-NF 32 with an official date of December 1, 2015.
• July-August 2014: The Expert Panel meets to make recommendations regarding any final revisions to revised General Chapters <232> and <233>. 
• Sept. 2014: General Chapters—Chemical Analysis Expert Committee meets to review Elemental Impurities Expert Panel recommendations and consider final revisions to revised General Chapters <232> and <233>. 
• October 2014: The General Chapters—Chemical Analysis Expert Committee ballots on the revised General Chapters <232> and <233>. 
• October 2014: USP pre-posts the approved revised General Chapters <232> and <233>, the Commentary, and a notice about the removal of General Chapter <231> on the USP Elemental Impurities Key Issues web page. 
• November 2014: All references to <231> in individual USP 38-NF 33 monographs are removed with official dates of December 1, 2015, which align with the applicability of <232> and <233> via General Notices 5.60.30.
• February 2015: The approved revised General Chapters <232> and <233> are published in the First Supplement to USP 38-NF 33, which publishes in February 2015 and becomes official August 1, 2015. 
• Aug. 1, 2015: The First Supplement to USP 38-NF 33 becomes official, including revised General Chapters <232> and <233> 
• Dec. 1, 2015:  General Notices section 5.60.30 becomes official, making <232> and <2232> applicable to drug product monographs. The Second Supplement becomes official, including the omission of General Chapter <231>.  

Source: US Pharmacopeial Convention