2008 was a watershed year in the FDA's oversight of Chinese drug ingredients. That was the year that contaminated raw heparin from China was tied to the deaths of dozens of U.S. dialysis patients, leading the FDA to realize it needed inspectors in China to oversee manufacturers. But a House investigation, launched that year and still ongoing, is questioning whether the FDA has done enough and whether the tainted heparin may still be getting into the U.S.
FDA Commissioner Robert Califf
In a 10-page letter to FDA Commissioner Robert Califf, the committee cites a story from FiercePharmaManufacturing to point out that French regulators recently discovered a Chinese company using what appeared to be tainted heparin. The company was getting its supplies from a Chinese company that is approved to import products to the U.S. and is not on the FDA's list of banned Chinese heparin suppliers.
It said there are also unresolved questions about whether Chinese suppliers may have used unapproved processes to try to remove oversulfated chondroitin sulfate (OSCS), a cheap but potentially deadly filler product, from heparin stockpiles and then recycle the products back into the U.S. It questions whether Chinese officials were complicit in allowing this.
The U.S. requires that raw heparin be made only from pig intestines to prevent contamination and that drugmakers that import it test for contaminants. But the committee says records indicate China is not slaughtering the number of pigs necessary to provide material for all of the raw heparin it exports to the U.S. That raises the question of whether some producers are using cow and sheep intestines to produce the raw material for heparin, which can lead to OSCS contamination.
"The concerns over foreign sourcing and the supply chain complexity of heparin also raise pertinent national security and biodefense issues," says the letter. It lists a series of what it considers failures by the FDA to fully investigate the 2008 episode. It also asks the agency to provide inspection reports from those Chinese heparin producers that have been inspected and to answer questions about what it is doing to prevent another episode of heparin contamination.
The letter follows a report filed last month by the European Medicines Agency (EMA) of France's inspection of Dongying Tiandong Pharmaceutical in Dongying City, Shandong Province. In that case inspectors uncovered data suggesting the drugmaker had manipulated tests of crude heparin supplies that had showed the presence of so-called ruminant DNA from cows or sheep. It said that there was no evidence that the samples used to do retesting came from the same batches that showed the ruminant.
The FDA uncovered a similar situation in 2014 during an inspection of China's Beijing Shunxin Meihua Bio-technical, putting it on its import alert list and issuing a warning letter. In that case, the FDA said the company appeared to be getting some of its raw materials from a supplier that is on an FDA watch list of suspect companies that don't carefully monitor the source of their materials. They were unable to do a thorough investigation because the company "repeatedly" refused to let inspectors into the production area or to review records.
- here's the letter