APP Pharmaceuticals ($APPX) has had its production of heparin called into question in an FDA warning letter and has been ordered to present three years worth of out-of-specification results for heparin and heparin lock flush.
The letter, dated Feb. 22 but posted this week, said APP, a subsidiary of Fresenius Kabi ($FRE), did not identify, at least to the FDA, why a batch of heparin lock flush manufactured at its Grand Island, N.Y., plant had failed an assay test. APP also did not show that it investigated whether other batches may have been out of spec.
"We are also concerned about a potentially related trend of OOS assay results for other batches of heparin active pharmaceutical ingredient (API) and Lock Flush," the FDA says.
In addition, the FDA said the company had not thoroughly investigated some customer complaints, including one "on March 1, 2010, citing dark particulate matter in a vial of Heparin." The letter does not make clear whether the dark particle in this case was an insect. It does say insects have been a problem in the sterile manufacturing area of the plant and showed up in vials of APP Pharmaceuticals products, including a vial that made it into distribution. The company's explanation was that the insects probably were introduced by a stopper supplier but then waited 16 months to audit the supplier.
The FDA, of course, is sensitive to heparin production. It has been soundly and repeatedly criticized for its oversight of global production of the injectable anticoagulant after the scandal in 2008 when hundreds of patients had allergic reactions and more than 80 died from injections of contaminated heparin. The heparin, marketed by Baxter International ($BAX), was found to be contaminated by active ingredient from China.
Last summer, a House subcommittee sent a letter to 10 heparin makers, including APP, asking for information about how such a serious contamination was possible. And just last week, the FDA identified another 14 Chinese companies that supplied contaminated materials to drug makers, bringing to 22 the number of Chinese suppliers on an import alert list.
The problems cited at APP Pharmaceuticals' plant didn't end with the failed batch of heparin. There are also reports of vials missing labels. The FDA also claims that the company is marketing some drugs that are not approved. APP refers to them as "five 'grandfathered' generic products with a total annual sales volume of approx. €15 million."
In a press release, Fresenius Kabi said it has made significant progress in addressing the problems, and that it expects to complete enhancements without disrupting output. It said it has full confidence in the quality of its products.
That would be bugs aside, of course.
- here's the FDA warning letter
- get the APP release