In the guidance the US Food and Drug Administration (FDA) calls on manufacturers to investigate the heparin supply chain to cut the likelihood of the crude material being adulterated intentionally.
“Know the identity and role of the actual manufacturer of crude heparin and any repackers and distributors who handle crude heparin before receipt and use”, the Agency wrote in draft guidance.
Manufacturers should audit their suppliers of heparin, both crude and API (active pharmaceutical ingredient) forms, to make sure they comply with cGMPs (current good manufacturing practices).
Testing should accompany increased oversight. Before using any crude heparin manufacturers should test each shipment for OSCS (oversulfated chondroitin sulphate), the contaminant linked to patient deaths in 2008.
“FDA has published an assay method for measuring OSCS contamination in crude heparin using strong anion exchange (SAX) high-pressure liquid chromatography”, the Agency wrote. Alternatives can be qualified for screening use but the SAX approach has already been evaluated for the test.
If OSCS is found, at any levels, manufacturers should reject and properly dispose of the heparin and tell the local FDA district office of the finding. The FDA also recommends following ICH (International Conference on Harmonisation) Q7 to prevent use of crude heparin containing OCSC.
Testing each shipment to confirm the species of animal the crude heparin originated from is also recommended. The test should be qualified for use with crude heparin and have enough accuracy, specificity, and sensitivity.
By running this test manufacturers can confirm their crude heparin is derived from pigs. Heparin can also be made from cows but the FDA wants to keep this out of products to prevent contamination with bovine spongiform encephalopathy (BSE), the neurodegenerative diseases known as mad-cow.