Heparin and Other Polydisperse Drugs: How To Monitor Their Safety

Heparin is a complex, polydisperse, microheterogenous polysaccharide drug that is widely used as a clinical anticoagulant.  In 2007-2008, an apparent adulteration of certain lots of heparin originating in China was associated with a number of adverse events some leading to patient deaths.  Our laboratory was part of an international group that aided in the discovery of the structure of the oversulfated chondroitin sulfate (OSCS) adulterant.  Since the heparin crisis our laboratory has focused on developing new methods and procedures to ensure the future safety of this critically important drug.  Among the lessons learned from the heparin crisis are:  1. The separation of the food chain from the drug chain; 2. The use of facilities operating under good manufacturing practices (GMP) with periodic regulatory inspections; 3. The introduction of anti-counterfeiting measures; 4. The development of improved analytical methods that can be implemented in quality assurance/quality control (QA/QC); and 5. A thorough and accurate record keeping.   The application of these lessens to heparin and other polydisperse drugs will be discussed.