Multiple heparin-producing factories in China may be subject to Detention without Physical Examination (DWPE) by the FDA, after the agency found that some firms may not conform to current good manufacturing practice (GMP) and may be inadequate in terms of safely preventing contamination.
This action follows the November 2010 voluntary recall by B. Braun Medical of a certain heparin sodium United States Pharmacopeia (USP) active pharmaceutical ingredient after it found traces of oversulfated chondroitin sulfate (OSCS) in injection products.
Now, the FDA said that heparin contaminated with OSCS indicates that the “methods used in or the controls used for the manufacture, processing, packing or holding do not conform to or are not operated or administered in conformity” with current GMP.
The FDA said that OSCS should not be part of the manufacturing process of heparin and added that OSCS is added intentionally to the drug for one reason—it is cheap. OSCS is also prepared by a simple synthetic process.
OSCS embodies similar properties to heparin that previously passed USP specifications for heparin sodium USP. In 2009, the USP revised monographs for heparin and incorporated tests that are able to detect the presence of OSCS.
In an addendum, FDA listed firms that may have varying forms of heparin.
“Since the article appears to be adulterated due to inadequate GMPs and is subject to Refusal of Admission per Section 801(a)(3) of the Federal Food, Drug and Comestic Act, FDA considers reconditioning or submission of analytical results to be insufficient to overcome the appearance of the violation,” the FDA said in a statement. Drugs offered by the firms in the FDA attachment are subject to DWPE until the FDA approves them and the violation is removed by either inspection, reinspection or submission of documentation.