Chinese Heparin Sourcing Questions Resurface After ANSM Inspection

Regulatory NewsRegulatory News | 01 March 2016 |  By 

France's National Agency for Medicines and Health Products Safety (ANSM) raised two critical deficiencies over a Chinese pharmaceutical company’s manufacture of heparin, which harkens back to the scandal from 2007 and 2008 when heparin sourced from Chinese manufacturers killed 149 Americans.

Following the December inspection of Dongying Tiandong Pharmaceutical Co.’s Dongying City-based manufacturing site, the site has been issued a statement of non-compliance and cannot be named on any marketing authorizations while the statement remains in place, according to the report on EudraGMDP.

ANSM said it uncovered 10 deficiencies, including two critical deficiencies:

  • [Critical 1] PCR (polymerase chain reaction) results of crude heparin "show the presence of ruminant DNA received from approved suppliers were manipulated. There was no evidence that the samples retested came from the same batch tested initially";
  • [Critical 2] The quality system implemented by the company for ensuring the full traceability of crude heparin "was identified as very weak : e.g., the traceability from slaughterhouses/abattoirs was not available and not assessed during the audits of the suppliers (lack of supporting documents for the received lots)."

Among the three major deficiencies, ANSM said the company misunderstood “the basic GMP principles for handling of out of specification (OOS) results and deviations (e.g., 7 batches of crude heparin received in 2014 and 2015 were obtained OOS for potency and used for the manufacturing of finished APIs without any OOS investigation).”

In addition, the company’s evaluation of the new suppliers of crude Heparin was deficient as “no delivery documents were available, the testing was not systematically recorded in the equipment logbook, the samples from approved suppliers were contaminated during the sampling operation, etc.”

Other identification tests for enoxaparin sodium were said to be deficient (for example, “the presence of an additional peak at the C13 NMR [carbon-13 nuclear magnetic resonance] obtained by a subcontracted laboratory was not identified and investigated.”)

“Consideration of a recall of product should be given due to the critical findings observed,” ANSM said.

Dongying did not respond to a request for comment and is not listed on the US Food and Drug Administration’s (FDA) import alert list.

But the notice of concern brings back concerns of previous heparin manufacturing inconsistencies in China. In October 2014, FDA warned a heparin manufacturer that refused access to its facility. That came after heparin sourced from Chinese manufacturers was linked to the deaths of 149, leading FDA to add 22 companies to its import alert list. But FDA has since raised concerns that some of those same companies are now circumventing its import alert ban by operating under new aliases and supplying their products to third parties.

ANSM Inspection Report


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