FDA Slams Conditions at Chinese Plant Implicated in Heparin DebacleApr 22, 2008 | Parker Waichman LLP
Conditions at the Chinese plant that produced a raw ingredient for tainted heparin have been deemed "unsuitable" by the US Food & Drug Administration (FDA), prompting the agency to send a strongly-worded warning letter to the factory. Raw ingredients supplied by the Changzhou, China plant were contaminated with a counterfeit ingredient, and have been implicated in 81 deaths in the US, as well as hundreds of adverse reactions.
Baxter International recalled nearly all its heparin injections in the US after some patients experienced extreme - and in some cases fatal - allergic reactions, including difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that was life threatening after being administered the products. There have been similar recalls by other manufacturers of Chinese-sourced heparin in Denmark, Italy, France Germany and Japan. In total, the FDA said tainted heparin has been identified in a 12 countries.
In March, the FDA confirmed that it had found oversulfated chondroitin sulfate in samples of the active ingredient used in Baxter heparin. The FDA said the chondroitin sulfate was molecularly changed to mimic heparin’s blood-clotting properties. That ingredient was supplied to Baxter by Changzhou SPL, a Chinese plant partially owned by Wisconsin-based Scientific Protein Laboratories. It costs a fraction of the ingredient usually used in heparin, and producers may have used it in an attempt to cut costs. Last week, FDA Commissioner Andrew von Eschenbach said that while the FDA has no specific evidence that the chondroitin sulfate contamination was intentional, “the concern is that it had to be by design.”
Due to computer error, the FDA never inspected the Chinese plant where raw ingredients for Baxter heparin were made. When heparin problems finally prompted the agency to conduct an inspection, it found a multitude of problems, including:
- Incomplete manufacturing instructions
- Lack of critical processing steps or annual test results
- Lack of an impurity profile for Heparin
- Incomplete manufacturing instructions for Heparin Sodium USP
- Investigations into failed lots were approved as complete, but no cause was listed
- Inadequate control of material flow in the processing area
Yesterday, a warning letter from the FDA to the Chinese factory was released. In the letter, the FDA said its inspection of the Chinese facility two months ago revealed "significant deviations" from US good manufacturing practices. In addition, the FDA said the plant's processing steps used to manufacturing heparin's active ingredient provided "no assurance" any impurities could have been effectively removed.
Scientific Protein Laboratories responded to the letter by claiming it does reflect Changzhou SPL's "actual state of compliance". The company also said the contaminant was introduced earlier in a supply chain. Changzhou buys its crude heparin from two companies, called consolidators, that gather it from workshops that make it from pig intestines. Many Chinese workshops that make crude heparin are unregulated family operations. Those workshop were apparently never inspected by the FDA either.