The US Food and Drug Administration (FDA) believes that the contamination of Baxter's blood thinner heparin, which has been linked to 62 deaths in the US, may have been due to the deliberate replacement of some ingredients with cheaper alternatives.
Analysis by the agency recently established that the drug lots in question contained oversulfated chondroitin sulphate, which is a less-expensive, animal cartilage-derived alternative to raw heparin that is not approved for use in medicine. Oversulfated chondroitin sulphate has been implicated in causing the hypersensitivity reactions associated with contaminated heparin.
FDA Commissioner Andrew von Eschenbach told the US Senate on Tuesday that the agency suspected the ingredient switch had been made "by virtue of economic fraud," but added that it would leave further investigation of the matter to Chinese State Food and Drug Administration officials.
Contamination early in supply chain
In response, Baxter and its active pharmaceutical ingredient (API) supplier, Scientific Protein Laboratories, said that the contamination occurred before the material had reached either company. Baxter, which initiated a product recall in February this year, is still investigating the issue.
Baxter spokeswoman Erin Gardiner said that "we know that over-sulphated chondroitin sulphate costs less than heparin," but added that "what we don't know is whether or not this was the motivation behind introducing a material that shouldn't be in a product."
SPL said that FDA and SFDA officials had not linked its facilities in either the USA or Changzhou, China with the contamination. The firm also said that "there was no possibility of economic benefit from SPL or CSPL," and added that its raw material costs had increased during the relevant period.
SPL also argued that reports from around the world suggest that contamination has been identified in products made by other manufacturers, indicating that the problem is widespread and must have occurred at a very early stage in the supply chain. Moves by European firms Opocrin and Rotexmedia to withdraw heparin products following the identification of contamination would seem to support this position.
However, Italy's Opocrin sources its raw ingredients from China's Shenzhen Hepalink Pharmaceutical, the same firm that supplies US-based heparin manufacturer APP Pharmaceuticals which has yet to identify contamination in any of its products.
No evidence, but strong suspicion
In a press meeting held after he addressed the Senate, von Eschenbach said that the presence of oversulfated chondroitin sulphate could not have arisen as a result of normal processing and formulation operations.
He added that while the agency has no specific evidence of such action, the replacement of heparin with oversulfated chondroitin sulphate could only have been carried out deliberately.
The FDA's announcement is its strongest to date and is part of an escalation in its response to the issue. Earlier this month, the agency unveiled plans to work with the United States Pharmcopeia Convention (USP) to develop more sensitive methods for detecting contaminants in heparin.