Abstract
The USP heparin sodium monograph lists impurities with specifications developed for porcine derived products. Most of these impurities are of biological origin and are present in porcine intestinal mucosa, the tissue source used in the production of porcine heparin. One of the specified impurities, oversulfated chondroitin sulfate (OSCS), has been introduced in the monograph to detect intended adulteration of heparin products with this impurity. The evaluation of bovine intestinal heparin as an alternative source of pharmaceutical heparin included an evaluation of bovine heparin with the current USP heparin sodium monograph methods. This evaluation included a comparison of impurity quantities observed in multiple bovine intestinal heparin samples against the specifications found in the USP heparin sodium monograph. The impurities investigated in this study were protein, galactosamine, nucleotidic impurities, and OSCS. Bovine intestinal heparin met the requirements in the tests for protein, galactosamine, and nucleotidic impurities. A potential issue was observed with the strong anion exchange high performance liquid chromatography (SAX-HPLC) used to analyze for the presence of OSCS. While the OSCS was well-resolved from the bovine heparin peak, the resolution of dermatan sulfate from heparin did not consistently meet system suitability requirements in the current USP Heparin sodium monograph. The overall levels of impurities observed in bovine intestinal mucosal heparin were comparable to those observed in porcine intestinal mucosal heparin. Bovine intestinal mucosal heparin can be produced with acceptable impurity levels that align with these important quality attributes found in porcine heparin.
Highlights
Heparin is a valuable animal-derived pharmaceutical that the medical community depends on to control blood coagulation in a number of patient applications
To evaluate whether the USP heparin sodium monograph analytical tests and limits for impurities could be applied to bovine intestinal heparin sodium active pharmaceutical ingredient (API), a study involving multiple laboratories was performed with the results provided in this report
This extraction step can result in residual proteins being present in the heparin that are removed through the purification steps associated with production of the heparin API
Summary
Heparin is a valuable animal-derived pharmaceutical that the medical community depends on to control blood coagulation in a number of patient applications. The need for porcine mucosa as the starting raw material for heparin production can lead to pressures on the supply chain that are not often not seen with pharmaceutical products produced through chemical processes. Those pressures can include disease, agricultural economics, and regional differences with regard to animal-derived protein sources (1). Occurring impurities found in porcine-derived heparin are defined by the USP heparin sodium monograph (3) with specific analytical tests and limits. Those impurities include galactosamine impurity, nucleotidic impurities, and protein impurities. To evaluate whether the USP heparin sodium monograph analytical tests and limits for impurities could be applied to bovine intestinal heparin sodium API, a study involving multiple laboratories was performed with the results provided in this report
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