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Fresenius Kabi, APP Pharmaceuticals division

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Company: Fresenius Kabi, APP Pharmaceuticals division
Plant: Grand Island, NY
Warning letter: Feb. 22, 2012

With the warning letter, APP Pharmaceuticals, a division of Fresenius Kabi, had its production of heparin and heparin lock flush called into question, after investigators found that the company did not do a thorough probe into why some batches failed assay tests. The result is that APP has been ordered to cough up three years of out-of-specification results for the two products.

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. Even Congress got involved and in the summer of 2011 sent a letter to 10 heparinmakers, including APP, asking for information about how such a serious contamination was possible.

The problems cited at APP Pharmaceuticals' plant didn't end with the failed batch of heparin, however. It also included the observation that APP had not thoroughly investigated customer complaints, including one of "dark particulate matter in a vial of Heparin." The letter does not make clear whether the dark particle in this case was an insect but does point out that the plant has an insect problem in the sterile manufacturing area and some of the bugs ended up in vials of heparin. The company's explanation was that the insects probably were introduced by a stopper supplier, but then it waited 16 months to audit the supplier.