Last updated: June 17, 2008
The Food and Drug Administration (FDA) has asked USP to aid in the revision of the heparin standards due to recent serious injuries and deaths associated with heparin containing adulterated active pharmaceutical ingredients from China.)
The Revision Bulletin is immediately official upon its posting (June 18, 2008) and all manufacturers who market heparin in the United States must meet these newly revised standards.
The Stage 1 revisions are intended to rapidly address the public health crisis and ensure a supply of heparin that is not adulterated. The Stage 1 revision has taken current FDA methods and improved the robustness of them. The Stage 2 revision will seek out more up to date methods. However, adapting current methods to create an expedited standard was the priority in Stage 1.
USP considers dermatan sulfate to be a process impurity that is present in heparin. Lower levels of dermatan sulfate indicate a better impurity removal process, but dermatan sulfate has not been linked to the deaths and injuries caused by adulterated heparin. Limits and test methods for dermatan sulfate will be addressed in the Stage 2 revision.
It has been improved by changing the concentration of heparin to 2mg/mL and changing the injection time to 30 seconds, from 10 seconds. These changes improve the resolution.
USP believes that both methods are needed to quickly allow for a qualified supply of heparin and to address the current adulteration of the heparin supply. This is an interim solution as Stage 2 begins. USP encourages any manufacturers that have methods for consideration in Stage 2 to submit them to Dr. Anita Szajek (email@example.com).
The current USP Heparin Sodium, Lot L, has not been affected by the revision; it is not for use in the new identity tests. USP Sodium Heparin RS is still for use in the sheep plasma clotting assay.
USP releases methods that have been validated with specific parameters. It is recommended that the methods be validated by manufacturers before use.
USP's heparin product monographs and LMWHs will be considered for revision in the Stage 2 revisions.