Two more Chinese companies linked to tainted heparin

Details continue to emerge about the convoluted heparin supply chain that brought the issue of substandard pharmaceutical ingredients in front of the public gaze in 2008.

In the latest development, the US Food and Drug Administration (FDA) has divulged that two Chinese companies shipped heparin contaminated with oversulphated chondroitin sulphate (OSCS) into the USA between 2007 and 2008, although the shipments were intercepted at the border.

The two companies are different from the one found to have supplied contaminated heparin to Baxter International last year. In that case the ingredient was supplied to Changzhou SPL, a Chinese facility partially owned by Wisconsin, USA-based Scientific Protein Laboratories.

At a Congressional hearing held last March, the FDA only identified Changzhou SPL by name, although at the time the agency said at least 12 Chinese companies had been implicated in the scandal.

The two new letters paint a stark picture of the shadowy nature of the trade with one company - Shanghai No. 1 Biochemical & Pharmaceutical Co. - operating as a front company while the other - Qingdao Jiulong Biopharmaceuticals Co. - actually made the material.

The details also provide further evidence of the need for pharmaceutical manufacturers to maintain tight visibility over their supply chains and audit suppliers carefully.

In the warning letter sent to Shanghai No. 1 Biochemical & Pharmaceutical Co, the FDA reveals that its inspection “revealed that the facility was not manufacturing, and did not appear to have ever manufactured ... heparin sodium for the US market.”

The agency’s investigators also determined that the company had explicitly lied in claiming that manufacturing of heparin sodium was conducted at the facility, which is cited in the Chinese firm’s drug master file (DMF) for heparin sodium.

The warning letter also said the FDA’s investigators “found that the manufacturers’ labels had been removed from the 5 kg bags during the repackaging operation and the bags were placed inside aluminium drums used to ship the heparin sodium to the US; the bags were then sealed and identified with the Shanghai No. 1 label.”

The two companies were involved in making and sending 19 lots of adulterated heparin sodium to the US, which the FDA discovered in April 2008. This occurred despite the fact that Shanghai No.1 “quarantined some of the contaminated material apparently produced by Qingdao Jiulong in 2008," according to the warning letters.

In January 2008, Baxter initiated a wide-ranging recall of its heparin products after some patients experienced serious – and sometimes fatal – allergic reactions after being administered the drugs. Similar recalls occurred in a number of European countries and in Japan.

The FDA has come under fire begun in the wake of the heparin scandal, with the US General Accounting Office concluding in April 2008 that while the agency was trying to step up inspections of overseas plants it was still falling short of what was required to guarantee consumer safety.

Since then, the FDA has opened offices in China and India and enacted a series of other measures, including tightened import controls, to try to improve supply chain security.