Last updated: June 17, 2008
We aim for the monographs to become official on August 1, 2009 after they have been approved by the USP B&B Blood and Blood Products Expert Committee. The final monographs will be published on the USP Web site prior to publication in USP’s Pharmacopeial Forum (PF).
Dialogue has been, and continues to be, ongoing between EP, JP, and USP regarding harmonization of some compendial tests.
Generally, USP does not publish validation work, though there are efforts to publish the work in the form of a peer reviewed article. If that occurs the article will be made available.
This would also require the inclusion of 'dummy' scans, prior to acquisition, in order to reach steady-state.
The USP Heparin Ad hoc Advisory Panel (AP) discussed the parameters in depth and the monograph reflects their decision. The sensitivity in the monograph test is sufficient to meet the requirements of the monograph.
The proposed Chromatographic Identity test is an orthogonal method that provides a clear separation of heparin from process impurities and OSCS.
Industry and members of the AP have helped to evaluate the methods and the specifications.
These were all data-driven decisions. The AP reviewed an extensive amount of past and current data from multiple lots of Heparin before deciding on the proposed specifications.
We have reviewed batch release data from the Heparin industry and regulators. The AP also generated additional data using commercially available Heparins to test the proposed specifications.
The specification was based on data from many commercial batches that were analyzed. We do not expect that it will cause good samples to fail.
USP has not seen many samples that have failed to meet this requirement. In the situation wherein a sample contains a large amount of residual solvent from the manufacturing process, there will be large solvent peaks in the region of 4.55–3.35 ppm. This will cause the sample to fail.
USP can not recommend a specific substrate; there are many suitable ones on the market. Each laboratory should evaluate the substrate(s) based on the platform of choice.
The AP has decided, and has also been encouraged by the FDA, to set the magnetic field strength requirement at NLT 500 MHz. It is at the regulator’s discretion to consider data from lower-field instruments.
If there are any signals in the 1H NMR spectrum consistent with OSCS that cannot be proven not to be OSCS, the sample fails, regardless of the signal height.
An ion chromatography system was used.
Yes, it does eliminate confusion. Most manufacturers run it with 13C decoupled.
The monograph requirements always supersede the general chapter requirements. Follow the monograph requirements.
LIMIT OF GALACTOSAMINE IN TOTAL HEXOSAMINE is the test for total galactosamine, not just dermatan sulfate, so a correlation is not intended.
USP releases methods that have been validated with specific parameters. It is recommended that the methods be validated by manufacturers before use.
There are no plans for the comment period to be extended.
The proposed USP Heparin Sodium RS, Lot M, will be released by the time the revised monograph becomes official (now planned for August 2009). This material will be calibrated against the current International Standard for Unfractionated Heparin to bring the USP Heparin Unit into harmony with the International Unit (IU). Future lots will be assayed against both the IS and the USP Reference Standard.