WASHINGTON, DC – Contamination concerns prompted the Food and Drug Administration (FDA) to send a warning letter to Chicago-based Abbott Laboratories and to ban shipping of the clot-busting drug Abbokinase. The government issued a letter in July saying Abbott Laboratories has not corrected safety problems that resulted in a shutdown late last year due to contamination from Hepatitis C and mycoplasma. [See “Contamination threat prompts FDA to add warning to urokinase shipments,” CleanRooms, March 1999, page 1.]
Kathryn C. Zoon, director for the FDA's Center for Biologics Evaluation and Research (CBER) writes in an 11-page document dated July 14 that the FDA received “new information that heightened the agency's concerns about deficiencies in the screening of the donors of the human neonatal kidney cells (HNK) used to manufacture Abbokinase.” Abbokinase is a proprietary form of the drug Urokinase, and is made from the kidney cells of stillborn or miscarried fetuses. It is used to dissolve blood clots in lungs and heart arteries and to clear catheter tubes. Although the FDA does not approve its use for blood clots in the legs, it is widely used for this.
FDA inspection reports say there was no documentation that the parents of newborns signed consent forms for use of the kidney tissue and that according to the reports, there was “no documentation of a questionnaire evaluating the suitability of the mother, nor documentation of an appropriate physical exam of the mother or neonate.”
The kidney tissue collected in Colombia was shipped to BioWhittaker, a Walkersville, MD cell-culture company, for further processing. FDA reports say, “BioWhittaker did not provide a description of the precautions taken to prevent adventitious contamination or cross contamination during the processing of the neonatal tissues and cells-kidney, liver, lung, central nervous system cells are harvested simultaneously in the South American facilities.”
According to the FDA, BioWhittaker then imported the materials into the United States without declaring them through customs as an FDA regulated-commodity and without being identified as “treat as potentially infectious.” These omissions violate U.S. law.
Noel Buterbaugh, president of BioWhittaker, says the problem was merely a labeling concern and the company had to change labels on the samples to comply with FDA regulations. He denies there was any contamination problem. He says there have been no problems in all the years his company has dealt with Abbott.
Buterbaugh says that his company is still trying to find a way to work with Abbott, but that difficulties with terrorism in Colombia would have halted the cell culture collecting program even if the FDA didn't. He reports that the doctor in charge of tissue collection at the hospital there was kidnapped recently, essentially ending the tissue collection there.
“Because of the political situation and the danger, we're not able to send people there to audit the collection program,” Buterbaugh says. “But we're optimistic that another source can be found.”
The FDA says Abbott has found six contaminated lots of Abbokinase containing reoviruses, mycoplasma and Hepatitis C during the past few months and asked the company to review and redesign its manufacturing process and to validate its viral inactivation tests.
Recall urged * Dr. Sidney Wolfe, Health Research Group director for the Washington, D.C. consumer advocacy organization Public Citizen, outlined his concerns in a letter February 10 to Dr. Jane Henney, FDA Commissioner, urging that Abbokinase be recalled. It wasn't. The FDA temporarily halted shipping, but allowed Abbott to continue manufacturing the drug.
Some lots were released in January and in late March. None have been released since. Melissa Brotz, Abbott spokeswoman says the company is continuing to work with the FDA on the situation. “The important thing right now is that we're working with the FDA on this,” she says. Last year, the FDA required Abbott to include this information on the Abbokinase label: “The kidney cells used in the manufacture of this product were obtained from populations at high risk of a variety of infectious diseases, including tropical diseases.”
Wolfe says the situation is the same since he wrote his letter in February, calling the FDA's failure to seize contaminated products and raw materials “a travesty.” Abbokinase should have been banned last year and all product should have been recalled,” he says. “FDA Washington overruled its own field inspection officers, caving in to pressure from doctors nationwide who used Abbokinase as a drug of choice. I don't know how much more evidence the FDA needs before it takes more drastic action.”
The FDA said a recall last year was not necessary because no illnesses had been reported. However, an FDA spokeswoman also said that illnesses were unlikely to have been reported, because many patients may not have associated symptoms with the drug. She said the risk of infection from taking the drug is unknown. The FDA has asked Abbott to locate the source of the contamination.
No contamination was found in any lots released to the public, and Abbott says that contaminated samples were not used in making the drug. However, the FDA has asked doctors to report any infections that could be attributed to Abbokinase. Most hospitals in the U.S. are out of Abbokinase, and the shortage is likely to continue.
Judy Keller