2008 Chinese Heparin Adulteration Litigation Lawsuit

2008 Chinese Heparin Adulteration Litigation

The product and the adulteration

Heparin is an injectable anticoagulant widely used in U.S. hospitals to prevent and treat blood clots. In 2008, the U.S. Food and Drug Administration (FDA) moved to recall heparin products after serious adverse reactions in patients were traced to adulterated raw material imported from China.

The affected batches were made by Baxter International, a pharmaceutical company that had subcontracted the manufacture of heparin precursor chemicals to Scientific Protein Laboratories. The subcontractor was a U.S.-registered company, but processing of the raw material took place in China, where heparin was extracted and processed from pig intestinal mucosa before being shipped to U.S. manufacturers.

Investigations by the FDA, academic institutions, and the companies involved identified the contaminant as over-sulfated chondroitin sulfate, a closely related molecule obtained from mammal or fish cartilage and commonly used in arthritis treatments. Because the over-sulfated form does not occur naturally, costs a small fraction of genuine heparin starting material, and mimics heparin's in-vitro behavior, it was not picked up by standard screening. Investigators concluded the substitution was almost certainly deliberate rather than an accidental lapse in manufacturing. The adulterated stock had been cut with chondroitin at varying levels, and the motivation was attributed to a combination of cost savings and a shortage of suitable pigs in mainland China.

Who was harmed

The FDA stated that at least 81 deaths were believed to be linked to the raw heparin ingredient imported from China, and the agency had also received 785 reports of serious injuries associated with the drug's use. Problems reported to the agency included difficulty breathing, nausea, vomiting, excessive sweating, and a rapidly falling blood pressure that, in some cases, led to life-threatening shock.

Investigation and litigation

In 2008 the FDA announced major recalls of heparin. A subsequent FDA inspection of the Chinese heparin supplier found significant deficiencies in the facility's quality systems, and the agency detailed those findings in a warning letter. Among other things, the facility had failed to monitor changes in the impurity profile of incoming heparin raw material, to adequately investigate out-of-specification results, to document actual processing steps in batch records, to validate all critical steps in the process, to qualify its suppliers, and to use valid methods to test products.

The episode also exposed a structural gap in oversight of imported active pharmaceutical ingredients. The FDA has stated that it lacks the funds and does not bear the responsibility to inspect overseas upstream processors of finished active pharmaceutical ingredients on a regular basis. Under the internationally harmonized ICH Q7 guideline, however, the responsibility for qualifying suppliers through on-site audits, testing, and regular communications rests fully with the API manufacturer.

Follow-on individual litigation emerged from the episode, and the source article notes that such suits remained pending at the time of writing.

Outcome

The adulteration episode closed in 2008 with the recall and the follow-on regulatory actions, including the warning letter to the Chinese supplier. The episode is recorded in this entry as a recall resolved in 2008.