- The Food and Drug Administration has issued a warning letter to a China-based manufacturer of a widely-used blood thinner.
- In the letter dated June 22, the agency called out Shandong Analysis and Test Center (SATC), which produces the active pharmaceutical ingredient (API) heparin, for not meeting current good manufacturing practices (cGMP). Specifically, the drug producer didn't disclose all the information that regulators asked for, and there were problems with its production practices.
- Researchers first discovered heparin about 100 years ago. Derived primarily from animal tissue, the molecule has long been used as an anti-coagulant, though it has also been at the center of a number of health concerns over the past decade.
U.S. regulators inspected the eponymously named SATC — located in Shandong, China — from Jan. 16 to Jan. 18. The facility is responsible for determining whether heparin and heparin-related drugs have over-sulfated chondroitin sulfate (OSCS), a contaminant that the FDA concluded back in 2008 was being intentionally added to heparin samples along the pharmaceutical supply chain as a means of reducing its production costs.
The agency flagged SATC for inadequately and infrequently testing the precision of its equipment used to analyze contamination in heparin samples.
While a Feb. 20 response from the manufacturer indicated it would more routinely check for system suitability, the FDA wasn't sold, and took issue with SATC not looking into the validity of the API produced under the previous protocols.
Other problems included SATC refusing to provide the FDA with test results of certain client's drugs without their consent, which in itself could cause the product in the facility to be deemed adulterated under the Food, Drug and Cosmetic Act.
Data access among the site's staff also raised concerns.
"During our inspection, we requested that you display original electronic data for analysis of heparin and heparin-related drug samples," the FDA wrote in the warning letter. "Your analyst was unable to retrieve requested data, and explained that he deletes older data to make space for newly acquired data."
Though all drugs and manufacturing practices fall under the FDA's scrutiny, the agency has kept a close eye on heparin in recent years following reports — some of which were fatal — of dialysis patients suffering serious acute hypersensitivity reactions after receiving heparin sodium.
As a result, the agency issued guidance in 2013 to pharmaceutical and medical device companies about how to best ensure the quality and safety of products that use the drug. Regulators warned against using any crude heparin that had any trace of OSCS, and to get the animal tissue from pigs rather than other sources.
"The potential for bovine heparin substitution, for example, could pose a risk because of possible contamination with the bovine spongiform encephalopathy (BSE) agent derived from ruminant materials," the FDA wrote in the guidance. "The control of the animal origin of crude heparin is important for ensuring the safety of drugs and devices that contain heparin and to protect public health."