Feb. 29, 2012 at 2:52 PM ET
In a move that highlights dilemmas plaguing the U.S. drug supply, federal regulators warned a major manufacturer about problems including bugs in vials of sterile drugs -- insects, literally -- the same day that health officials allowed the firm to ramp up scarce medications for kids with cancer.
Food and Drug Administration officials on Tuesday posted a warning letter sent to APP Pharmaceuticals LLC of Schaumberg, Ill., citing violations at a New York plant that included insects found in clean rooms and in vials of distributed drugs and failure to report defects such as vials contaminated with foreign matter and glass.
The firm also had problems with documenting sterile technique and was marketing unapproved drugs, according to the warning.
“It is apparent that APP Pharmaceuticals LLC’s has failed to implement global corrective actions,” it said.
The letter was dated Feb. 22, the same day that APP announced it had received accelerated FDA approval to market supplies of preservative-free methotrexate to help ease a critical shortage of the medication used to treat childhood leukemia.
Earlier this month, FDA officials and cancer doctors had said the drug was in such short supply, hospitals could have run out within two weeks, jeopardizing life-saving treatment for kids with acute lymphoblastic leukemia, or A.L.L., as well as patients with other illnesses.
“I am delighted that in many cases APP Pharmaceuticals has helped to minimize shortages by significantly increasing our production,” John Ducker, the firm’s president and chief executive said in a statement last week. APP Pharmaceuticals is a subsidiary of the German firm Fresenius Kabi Pharmaceuticals Holding Inc.
The timing was not lost on Erin Fox, manager of the Drug Information Service at the University of Utah, which tracks the nation’s drug shortages.
“This is what I mean when I keep talking about quality issues,” said Fox, citing ongoing manufacturing problems at several U.S. plants, including APP. “All of these companies have had quality issues, yet they make the majority of drugs used in our country.”
The U.S. has logged record numbers of drug shortages in the past two years, fueled in part by sudden closures of drug plants because of problems with contamination, crumbling infrastructure and other issues, FDA documents show.
APP officials said the warning letter, which focused on problems at the firm’s Grand Isle, N.Y., plant, and the company’s efforts to ease the drug shortage crisis were two different issues.
“Methotrexate is not manufactured at the Grand Island plant and, thus, is absolutely unaffected from the warning letter,” Matthias Link, a company spokesman, wrote in an e-mail to msnbc.com.
The violations followed an FDA inspection last summer, June 13 to July 8, and the company had “already begun taking actions on most of the items listed,” Link noted.
“We take all the issues listed in the warning letter very seriously and we are committed to promptly addressing these,” he wrote.
The firm has 15 days from the date of the FDA letter to respond to the problems, including how insects came to be found in an aseptic, or sterile, room used to produce crucial drugs.
“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.
Company officials told FDA inspectors the root cause of the bug problem was with the firm’s supplier of gowns, but they had not scheduled an audit of the firm until six months later, December 2011, the warning said.
FDA officials did not immediately respond to msnbc.com questions about the timing of the warning letter and the expanded approval of APP to make injection-free methotrexate.
Agency officials last week announced they’d narrowly averted two dire shortages: first, the methotrexate scarcity, and then an ongoing shortage of the drug Doxil, used to treat ovarian and other cancers.
The agency licensed a foreign firm, Sun Pharma, temporarily to supply Lipodox, a replacement chemotherapy drug, to the U.S. market.
Balancing the demand for life-saving drugs with the demand that those drugs be safe and sterile is an ongoing challenge, noted Fox.
“Between the shortages and the quality issues, it is difficult to have any kind of confidence in our drug supply,” she said.