12-14 December 2023
The USP published on 1st February 2013 the two General Chapters <232> "Elemental Impurities - Limits" and <233> "Elemental Impurities - Procedures". Section 5.60.30 of the "General Notices" - which has been revised and whose publication should be made in the USP 37-NF32 on 1st May 2014 - links both chapters to drug product monographs. In a press release posted on its website on 24 May 2013, the USP announced the deferral for an indefinite period. As section 5.60.30 will not be included in the "General Notices" there is no requirement for any drug product in the USP-NF to comply with <232> and <233>. Although these chapters were officially published and are in force since 1st February, they are now kind of "orphan". In this context, the proposed omission of General Chapter <231> Heavy Metals also has been deferred too.
The cause for the deferral is convincing and explained in the notice from 24 May. The USP wants to react to the numerous comments which were sent after publication of the draft of revised section 5.60.30 in the Pharmacopeial Forum 39(1) from January 2013. Many of these comments referred to the forthcoming publication of the ICH Q3D "Guidance on Limits for Metal Impurities", awaited in June 2013 - and the necessary harmonisation with ICH Q3D which still exists as Concept Paper but should (if it's published as Step 2 document soon) set binding limits for metallic impurities, procedures for their calculation, methods for risk evaluation and further technical details for the three economic regions: Europe, USA and Japan. To avoid inconsistency in the approach for controlling metallic impurities, the USP wants to align the General Chapters with the ICH Q3D Guideline and needs more time for it. Further questions regarding this quite sudden deferral were published in a Question & Answer document on 29 May 2013 on the USP website.
The USP hasn't yet set a new date for the publication of the revised sections 5.30.60. The USP has an observer status in the ICH. In the course of the ICH process, it will work closely with the ICH committees to quickly adjust the USP Chapters. The USP Council of Experts - which is responsible for the implementation of section 5.30.60 - will be supported by an "Advisory Group" composed of FDA and industry representatives with regard to the implementation timing.
The necessary adjustments with the new ICH Q3D Guideline also concern the USP Chapters about Arsenic (<211>), Lead (<251>) and Mercury (<261>). As certain USP-NF monographs refer to these chapters, the USP will also revise them thoroughly.
USP monographs for veterinary medicinal products are not concerned by this topic. In the FAQ document, the USP recommends manufacturers of veterinary medicinal products to address their questions about the monitoring of metallic impurities directly to the FDA.