Quality Problems At Drug Plants Fuel Shortages

Quality problems at drug plants are fueling shortages of critical medications, including pediatric cancer drugs.

Federal regulators warned a major drug manufacturer about problems, including a disturbing issue involving bugs in vials of sterile medications, said MSNBC. This, on the same day health officials allowed the drug maker to increase production of a limited drug for children with cancer.

Officials with the U.S. Food and Drug Administration (FDA) posted its warning letter to APP Pharmaceuticals LLC of Schaumberg, Illinois. The letter cited violations at a New York plant such as insects found in “clean rooms” and in vials of drugs that had been distributed, as well as APP’s failure to report defects, including vials contaminated with glass and other foreign matter; problems documenting sterile technique; and marketing unapproved drugs, wrote MSNBC. “It is apparent that APP Pharmaceuticals LLC’s has failed to implement global corrective actions,” the letter said.

Dated February 22, the letter was written on the same day APP made an announcement it received accelerated FDA approval to market preservative-free methotrexate in response to a serious shortage of the childhood leukemia medication, said MSNBC. FDA and oncologists said methotrexate was so limited that hospitals could use all their supplies within a matter of weeks. This was in early February. The drug is considered a life-saving therapy for children suffering from acute lymphoblastic leukemia (ALL), among other patients and illnesses, explained MSNBC.

“I am delighted that in many cases APP Pharmaceuticals has helped to minimize shortages by significantly increasing our production,” John Ducker, APP’s president and chief executive said, wrote MSNBC. APP Pharmaceuticals is a subsidiary of Fresenius Kabi Pharmaceuticals Holding Inc. of Germany.

But the drug shortage and contaminated drugs are two different issues. “This is what I mean when I keep talking about quality issues,” said Erin Fox, manager of the Drug Information Service at the University of Utah, which tracks the nation’s drug shortages, wrote MSNBC. “All of these companies have had quality issues, yet they make the majority of drugs used in our country,” Fox added.

“You continued to find insects in your manufacturing area, in finished product (two vials), and you received a complaint for an insect in a distributed vial,” said the letter sent by Ronald M. Pace, director of the FDA’s New York district, according to MSNBC.

APP’s production of heparin is also at issue with the FDA, which ordered APP—in its February 22 letter—to supply it with out-of-specification results for heparin and heparin lock flush for the past three years, said FiercePharma The drugs failed an assay test. “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 said.

The FDA also said the APP neglected to fully investigate customer complaints, such as one “on March 1, 2010, citing dark particulate matter in a vial of Heparin,” reported FiercePharma. Reports of vials missing labels and other issues were also discussed in the letter, said FiercePharma.

APP has 15 days from the date of the letter to respond to the problems and explain how bugs ended up in an aseptic “clean” room in which critical drugs are produced.