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 USP Heparin InformationLast updated: October 2, 2009 What's NewOctober 2, 2009
The second stage of USP's revisions to quality standards for the widely used blood thinner heparin became official on October 1, 2009 (see list below). The Stage 2 revisions, discussed further below, include new methodologies for identification, the implementation of a new potency assay and additional tests for impurities. In addition, the heparin potency unit has been harmonized with the International Unit (IU)). For more information on the new potency assay and effect of the change in potency assignment, please see USP Statement on Heparin Potency Unit Assignment and Harmonization with the International Standard for Unfractionated Heparin below and information provided by the FDA at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm184502.htm. Now Official: Stage 2 Heparin Sodium Monographs and Related Monographs with Conforming Changes
August 21, 2009 USP Statement on Heparin Potency Unit Assignment and Harmonization with the International Standard for Unfractionated Heparin In response to the heparin adulteration crisis of 2007/2008, USP has worked swiftly to improve the standards for unfractionated heparin (UFH) in order to secure the supply of safe heparin and heparin products in the US. As part of the Stage 2 revisions to the Heparin Sodium monograph, USP has adopted a new potency assay for heparin, the chromogenic anti-Factor IIa test. The high specificity of this assay provides an additional safeguard against potential adulterants that may display heparin-like activity in the previous USP plasma-based assay. Transition to the new assay and parallel introduction of a new potency reference standard, USP Heparin Sodium for Assays Reference Standard, has given the USP the opportunity to calibrate the new material relative to the International Standard (IS) for UFH issued by the World Health Organization (WHO). Over the past 30 years, there has been an estimated drift of 10% between the USP heparin unit and the international unit for UFH. The calibration of the new USP Heparin Sodium for Assays Reference Standard eliminates this difference since the standard is directly traceable to the 5th IS for UFH. USP does not anticipate that the change in the USP heparin unit resulting from its harmonization with the IS has clinical significance. Due to the inherently low and extremely variable bioavailability of heparin, finished drug product potencies are generally specified with ±10% of the potency values. In addition, therapeutic dosing of heparin is generally monitored by aPTT. However, USP encourages industry stakeholders to work closely with the Food and Drug Administration and the medical community in communicating the change in potency assignment. Heparin Monograph RevisionsUSP's heparin sodium monograph, official since 1950, has been revised several times since then. In 2006 the Heparin Ad hoc Advisory Panel was formed to focus on development of a new potency assay. Subsequently, following reports of the prevalence of contaminated heparin products that resulted in more than 200 deaths and in response to a request from FDA to update USP monographs for Heparin Sodium and Heparin Calcium following heparin recalls in early 2008, Stage 1 revisions aimed at helping to ensure a safe Heparin supply were completed and became official via Revision Bulletins posted on USP's Web site on June 18, 2008. The USP Heparin Ad hoc Advisory Panel, which reports to the USP Biologics and Biotechnology Blood and Blood Products Expert Committee (BBP EC), recommended that additional changes be implemented to further strengthen the Heparin monographs. These Stage 2 revisions were presented in Pharmacopeial Forum (PF) 35(2) March-April 2009 as proposed Interim Revision Announcements (IRAs). After public and review and comment, and subsequent recommendations by the Advisory Panel, the BBP EC approved the revisions. These revisions have appeared in PF 35(5) and have become official as of October 1, 2009. The Stage 2 revisions include new methodologies for identification, the implementation of a new potency assay and additional tests for impurities. In addition, the heparin potency unit has been harmonized with the International Unit (IU)). Additionally, the BBP EC has made conforming changes to the following monographs: Anticoagulant Heparin Solution, Antithrombin III Human, Heparin Calcium, Heparin Calcium Injection, Heparin Lock Flush Solution and Protamine Sulfate. As part of the Stage 2 revisions to the Heparin Sodium monograph, USP has adopted a new potency assay for heparin, the chromogenic anti-factor IIa test. The high specificity of this assay provides an additional safeguard against potential adulterants that may display heparin-like activity in the current USP plasma-based assay. Transition to the new assay and parallel introduction of a new potency reference standard, USP Heparin Sodium for Assays Reference Standard (RS), has prompted USP to align all heparin monographs with the newly revised Heparin Sodium monograph. The new potency RS has been added to General Chapter <11> Reference Standards. These Revision Bulletins replace current USP Heparin Sodium RS with the new USP Heparin Sodium for Assays RS for Anticoagulant Heparin Solution, Antithrombin III Human, Heparin Calcium, Heparin Calcium Injection and Heparin Lock Flush Solution. An extensive revision for USP Protamine Sulfate monograph is planned in the near future. In the interim, the Assay for USP Protamine Sulfate will continue to utilize current USP Heparin Sodium RS as well as Plasma preparation, which has been moved from Heparin Sodium monograph to Protamine Sulfate monograph. The Revision Bulletins for Anticoagulant Heparin Solution, Antithrombin III Human, Heparin Calcium, Heparin Calcium Injection, Heparin Lock Flush Solution, Protamine Sulfate supersedes those in USP 32–NF 27. The Revision Bulletin text will be incorporated into the First Supplement to USP 33–NF 28. The following table summarizes the Stage 1 and 2 revisions:
Reference StandardsIn addition to the USP Heparin Sodium RS, USP Heparin Sodium Identification RS and USP Endotoxin RS, USP has developed four new reference standards to support the new methods for identification and impurity tests in the heparin monographs. One of the new USP Reference Standards, Heparin Sodium for Assays RS (Lot F0I187), is now available and became official on October 1, 2009. This reference standard will be used for the Anti-factor Xa activity test and the new Anti-factor IIa potency assay. USP Heparin Sodium RS (Lot L1I033) will be used solely for applications in the Protamine Sulfate drug substance and drug product monographs. Now Available
If you would like to receive email notifications when these new, first time Reference Standards become available, sign up for USP's Reference Standards Release Notification Program. Download the entire USP Reference Standards Catalog. Stage 1 Monograph Revisions (Please see Accelerated Revision History Section) Additional Information
Media Information
USP's Compendial UpdatesTo keep informed about any Revision Bulletin to the USP Heparin monographs, sign up for USP's free Compendial Updates email service. Sign-up to ReceiveContactsMonographs: Anita Szajek, Ph.D. () Related Links |
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