The US Food and Drug Administration (FDA) released a warning letter on Wednesday for China-based heparin contract testing lab, Shandong Analysis and Test Center, reigniting a debate over whether the questionable sources of heparin that led to almost 100 American deaths a decade ago have been rooted out.

Background

In 2007 and 2008, heparin sourced from Chinese manufacturers was linked to the deaths, though House Energy & Commerce committee members expressed concerns on FDA delays to import alerts issued to more than 30 Chinese firms producing contaminated heparin.

Since 2012, FDA has finalized guidance recommending practices for monitoring the quality of crude heparin and the US Pharmacopoeia (USP) has released heparin quality standards meant to boost safety and quality.

In 2014, Beijing Shunxin Meihua Bio-technical Co., Ltd., a manufacturer of heparin active pharmaceutical ingredients (APIs), received a warning letter after it barred FDA inspectors from accessing parts of its manufacturing site. 

Questions of contamination also resurfaced last year when French regulators and later FDA warned a Shandong, China-based company for using crude heparin batches that potentially were out of specification.

Warning Letter

Now, another Shandong-based company is being cited in an FDA warning letter, this time a contract testing lab that analyzes samples of heparin and heparin-related drugs for the presence of over-sulfated chondroitin sulfate (OSCS) using Nuclear Magnetic Resonance (NMR) spectroscopy. 

FDA previously agreed that OSCS was a contaminant in the heparin that caused adverse events during the crisis from 2008.

"You failed to routinely establish system suitability when testing samples for OSCS," FDA said in the warning letter dated 22 June 2017. "Furthermore, on December 26, 2014, you conducted a system suitability test that failed. You did not investigate why your equipment failed system suitability for detection of OSCS, or determine the reliability of other OSCS tests conducted prior to the date of the system suitability failure."

In addition, FDA said the lab’s "quality control unit did not have basic controls" to prevent changes to electronic lab data. And one of the company's analysts "was unable to retrieve requested data, and explained that he deletes older data to make space for newly acquired data."

FDA also found that the company "failed to provide information pertaining to samples analyzed" by a specific firm (the name of the company has been redacted) "that produces heparin and heparin-related drugs for the U.S. supply chain."

Warning letter for Shandong Analysis and Test Center 6/22/17