The Food and Drug Administration announced on Feb. 21 that it had lined up several manufacturers that can provide enough doxorubicin and methotrexate to alleviate current shortages of these vital cancer drugs starting immediately.
Doxorubicin has been in short supply off and on for the last several years. It is approved for use in AIDS-related Kaposi’s sarcoma, multiple myeloma, and ovarian cancer.
Shortages of methotrexate date back at least 5 or 6 years. The most recent methotrexate shortage – which began in November, when the main manufacturer, Ben Venue Laboratories in Bedford, Ohio, had to go off-line due to quality issues – has had an impact on the treatment of acute lymphoblastic leukemia, according to the agency and pediatric oncologists. The New York Times reported on Feb. 10 that hospitals could start running out of methotrexate within 2 weeks.
The restoration of supplies of both drugs "is all good news for patients," said FDA Commissioner Margaret Hamburg at a briefing with reporters. Dr. Hamburg and other FDA officials touted the agency’s proactive moves in addressing the shortages.
For doxorubicin (Doxil), the FDA began looking for alternative manufacturers, although agency officials did not say when. At least one company, Sun Pharma Global FZE, made the drug overseas, said Dr. Sandra Kweder, deputy director in the FDA’s Office of New Drugs, at the briefing. That version of doxorubicin – called LipoDox – is not yet approved in the United States, but the FDA is allowing temporary importation.
The move is largely possible because the company received previous FDA approvals and thus has been subject to FDA inspection before, said Dr. Kweder. "We feel confident in the safety and utility of this product," she said.
With methotrexate, the drug shortage team began working with alternative manufacturers, including Hospira, Mylan, and Sandoz Pharmaceuticals, when Ben Venue began having issues, said Dr. Hamburg.
Ben Venue accumulated some emergency supplies before its shutdown; those will be released soon. Still, it was evident there could be a dire shortage, said Dr. Hamburg.
Preservative-free methotrexate was especially needed for pediatric uses.
Schaumburg, Ill.–based APP Pharmaceuticals is another of the companies that stepped up to help deal with the shortage. The company first ramped up production of methotrexate with preservative, said Mitchell Ehrlich, vice president for quality assurance at APP.
APP then worked with the FDA to expedite review of a generic drug application to produce preservative-free methotrexate. That application was approved on Feb. 17. The company will begin supplying the preservative-free formulation within 4 to 6 weeks, said Mr. Ehrlich.
Hospira, based in Lake Forest, Ill., also ramped up supply and began shipping on Feb. 21, starting with 31,000 vials. That is a 1-month supply, said CEO Michael Ball, at the briefing. The week of Feb. 27, the company will release an additional 34,000 vials, he said. That should be enough to provide a cushion while other companies come on-line.
ASCO: More Needs to Be Done
Also on Feb. 21, the FDA issued draft guidance directing manufacturers and distributors on processes for notifying the agency of problems that could potentially lead to shortages.
At the briefing, patient and physician organizations applauded the FDA’s actions. But they also said that more needs to be done.
Dr. Michael Link
"Many other drugs remain in shortage and we need permanent solutions," said Dr. Michael Link, president of the American Society of Clinical Oncology. He called on Congress to appoint a joint House-Senate working group to build on legislation making its way across Capitol Hill and come up with a permanent solution within 60 days.
As part of that solution, ASCO is also seeking a requirement that all manufacturers give advance notice of potential shortages, at least 6 months in advance or as soon as such problems become known. It also wants Congress to provide incentives for companies to develop contingency plans, or to encourage manufacturers to continue to produce drugs, if they are essential and susceptible to shortage. Finally, Dr. Link called on Congress to pass a law establishing generic user fees.
Children’s Oncology Group: Give Us a Law Within 4 Weeks
Dr. Peter Adamson, chairman of the Children’s Oncology Group, was more blunt. "I understand that passing legislation is complex and difficult," he said. "I suspect, however, that it is no more difficult than curing a child with cancer." He challenged lawmakers to enact a solution within four weeks.
Dr. Leonard Lichtenfeld
"The encouraging news we heard today is not the end of this story. There are potential future crises waiting to happen," said Dr. Adamson.