Amid indications that more people may have died or been harmed after being given a brand of the blood thinner heparin, federal drug regulators said Thursday they had found “potential deficiencies” at a Chinese plant that supplied much of the active ingredient for the drug.
Baxter International, which makes the brand of heparin associated with the problems, and buys its supplies from the Chinese plant, announced it was expanding a recall to include virtually all its heparin products. Though Baxter produces much of the heparin used in the United States, regulators said the other major supplier would be able to meet the demand.
The Food and Drug Administration said the number of deaths possibly associated with the drug, made from pig intestines, had risen to 21 from four. But it cautioned that many of those patients were already seriously ill and that the drug may not have caused their deaths.
The FDA emphasized that it had yet to identify the root cause of the problem, and that it had not concluded that the Chinese factory was responsible. The agency also said it was investigating two Chinese wholesalers — also called consolidators — that supplied crude heparin to the Chinese plant, Changzhou SPL, as well as those who sold raw ingredients to the consolidators.
The New York Times reported Thursday that at least one of the consolidators received supplies from small, unregulated family workshops that scraped mucous membrane from pig intestines and cooked it, eventually producing a dry substance known as crude heparin.
The FDA admitted earlier this month that it had violated its own policy by failing to inspect SPL, located west of Shanghai, before it began shipping the heparin ingredient to Baxter in 2004. China’s drug agency also did not inspect the plant.
Last week, the FDA sent inspectors to the plant. Among the potential problems they found was a failure to properly follow the steps for identifying impurities and deficiencies related to manufacturing equipment. According to a redacted inspection report released by the agency, the SPL plant appeared to have made at least some heparin with “material from an unacceptable workshop vendor.” The vendor was not identified.
Scientific Protein Laboratories, a Wisconsin company that is the majority owner of the Chinese plant, issued a statement on Thursday saying the FDA’s finding did not represent its final determination as to whether the plant complied with federal regulatory rules. The company, the statement said, is committed to finding the root cause of the adverse reactions.
Erin Gardiner, a spokeswoman for Baxter, said the company was reviewing the FDA’s report. “We expect SPL to respond to those observations thoroughly and promptly,” Gardiner said. “The observations are important and need to be addressed promptly but they are not necessarily indicative of the root cause.”
The FDA concern’s about heparin had previously centered on Baxter’s multidose vials, but on Thursday Baxter agreed to voluntarily recall not only the multi-dose vials but also single-dose vials and a diluted solution of heparin used to keep blood clots from forming in intravenous lines. There have been no adverse reaction reports involving the latter product, called Hep-Lock heparin flush products.