FDA has released a draft guidance for API manufacturers titled Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality. The guidance was issued in response to a 2008 incident in which heparin sourced from China was adulterated with oversulfated chondroitin sulfate (OSCS), causing serious adverse reactions in patients.

The draft guidance is intended to alert manufacturers of APIs, pharmaceutical and medical-device manufacturers of finished products, repackers, and others to the potential risk of crude heparin contamination. In addition, it offers guidance for identifying and responding to adulterated crude heparin. FDA defines crude heparin as an unrefined mixture of heterogeneous polysaccharides including various impurities isolated from mammalian tissues that requires further purification and processing before clinical use.

According to the guidance, FDA considers the presence of OSCS or any nonporcine origin material, especially ruminant material (unless specifically approved as part of the drug application) in crude heparin, or any other form of heparin, to render that drug adulterated under section 501 of the Food, Drug and Cosmetics Act (21 92 U.S.C. 351).

The draft guidance contains recommendations for procedures to ensure that crude heparin does not contain OSCS or nonporcine origin material, including:

• Testing and confirming the species of origin of crude heparin in each shipment
• Testing for OSCS sulfate in each shipment
• Knowing and identifying the actual manufacturer of crude heparin as well as any repackers or distributors who handle it before receipt and use
• Employing the controls described in ICH Q7 to prevent the use of adulterated heparin, and fully and promptly investigating and resolving any deviations in quality
• Rejecting and properly disposing of any adulterated crude heparin, as well as notifying FDA of the finding.

Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.

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