The FDA has issued a warning letter to a Chinese heparin maker for some of the same kinds of issues raised by the EU, which earlier acted against the company for manipulating data in its manufacturing of the blood thinner.
In a warning letter delivered this month and posted Tuesday, the FDA said that during an inspection of the Dongying Tiandong Pharmaceutical plant in Dongying City, Shandong Province last year, inspectors found that the company had repeatedly retested crude heparin batches when they tested out of spec for ruminant DNA.
“You neither evaluated the initial sample OOS, nor conducted retesting of the initial original sample to confirm it. Instead, you resampled until you obtained a passing result,” the FDA letter said. “Disregarding the OOS results, and resampling and retesting without scientific justification, constitutes ‘testing into compliance.’ This practice is unscientific and objectionable under CGMP."
That is an essential test because FDA rules require heparin to be manufactured only from pig intestines because when "ruminant" animals like cattle are used, there is a chance the raw material could be contaminated with bovine spongiform encephalopathy (BSE).
The FDA also questioned the company’s test for validating crude heparin from suppliers, important for the same reason. It said that it did reject suppliers whose crude failed testing, but if it had a supplier that it had already qualified but whose shipment “failed ruminant DNA testing, you did not reject the material and reevaluate the raw material supplier’s qualification status,” the FDA said.
Earlier this year, the European Medicines Agency yanked the certificate of compliance from Dongying Tiandong after French inspectors uncovered data suggesting the drugmaker had manipulated tests of crude heparin supplies that had shown the presence of ruminant DNA. It said that there was no evidence that the samples used to do retesting came from the same batches that showed the ruminant.
The report issued by the European Medicines Agency said the company’s “Misunderstanding of the basic GMP principles” resulted in 7 batches of crude heparin being used to make finished APIs without ever being investigated for out-of-specification potency."