Both FDA and EMA have issued guidance for industry focused on the control of the biological starting material, porcine mucosa, used to manufacture heparin, that clarifies testing and supply chain expectations.
FDA’s draft guidance on “Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality” outlines the importance of using tests for contaminants that complement the required USP monograph tests. The draft stresses the need for suitable tests to detect the contaminant oversulfated chondroitin sulfate (OSCS) as well as “the use or development of methods” to test for the presence of material derived from ruminant animals that may contain bovine spongiform encephalopathy (BSE) agents. Comments are due by April 13.
In addition to raw heparin, EMA’s “reflection paper” covers starting materials that are derived from plasma or urine. The paper focuses on defining and testing the materials and ensuring their equivalence when derived from multiple sources. Comments are due by the end of August.
The lethal health implications of the 2008 OSCS contamination helps explain the emphasis that European regulators have been placing during the review process on the importance of starting material definition and control (IPQ “The News in Depth” March 21, 2011).
Industry, on the other hand, particularly on the drug chemical side, has been cautioning an overemphasis by regulators on the starting materials misses the greater impurity threats that enter later in the API and finished dosage manufacturing contexts and create roadblocks to API processing upgrades (IPQ “The News In Depth” March 20, 2012).
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