Regulatory Focus™ > News Articles > With Eye on Tainted Chinese Heparin Scandal, FDA Finalizes Quality Monitoring Guidance

With Eye on Tainted Chinese Heparin Scandal, FDA Finalizes Quality Monitoring Guidance

Posted 26 June 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has released a finalized guidance document recommending certain practices for monitoring the quality of crude heparin, a response to systemic failures in quality monitoring in 2007 and 2008 that resulted in the deaths of nearly 150 Americans.

Background: Scandal and Death

The final guidance is similar to one released in February 2013 and aims to "help active pharmaceutical ingredient (API) manufacturers, pharmaceutical and medical device manufacturers of finished products, repackers, and others to better control their use of crude heparin that might contain oversulfated chondroitin sulfate (OSCS) or non-porcine material (especially ruminant material) contaminants."

The need for the guidance can be traced back to 2007 and 2008, when heparin sourced from Chinese manufacturers killed 149 US citizens. While FDA would ultimately link nearly 22 Chinese companies with the manufacture of that heparin, it has also been placing more of an emphasis on the responsibilities of contacting entities to test and verify the identity of products that come into their possession.

As an interim measure, the US Pharmacopoeia (USP) released heparin quality standards in 2012 meant to boost the safety and quality of the drug. "In response to requests from the FDA, USP has identified and plans to incorporate into the standards new and improved procedures and tighter specifications for detecting and deterring the presence of OSCS as well as improved control for protein and nucleic acid impurities," USP wrote at the time.

OSCS, presumed to be derived from animal cartilage, was identified as a primary contaminant in the scandal, and FDA said it remained "concerned about the potential for contamination of heparin" with OSCS and other ruminant materials.

Final Guidance: The Basics

"The control of the quality of crude heparin is important to ensure the safety of drugs and devices and to protect public health," FDA added in a Federal Register notice announcing the final guidance. "FDA developed this guidance to alert manufacturers to the risks of crude heparin contaminants and to recommend strategies to ensure that the heparin supply chain is not contaminated with OSCS or any non-porcine ruminant material (unless specifically approved as part of drug or medical device application)."

The final guidance makes several recommendations, including:

  • that manufacturers test and confirm the species origin of crude heparin using a qualified testing method before it is used in the manufacturing process of a drug or device
  • that all heparin lots should be tested for OSCS before use, again using a qualified test method
  • all heparin lots should be tested for other ruminant mucosa. Lots found to contain such ruminants should be rejected and FDA alerted to the finding
  • heparin suppliers should be audited on a regular basis to "ensure conformance to appropriate quality standards."

Manufacturers should comply with the International Conference on Harmonisation's (ICH) Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients guideline, as well as quality system regulations under 21 CFR 820 if the product is a medical device.

The guidance is immediately effective, as it does not create any new obligations for industry.


Guidance for Industry: Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality

Federal Register


Tags: Heparin

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