The U.S. Food and Drug Administration took steps on Feb. 21 to reverse shortages of two key cancer drugs—using its enforcement discretion to allow the import of the chemotherapy agent Lipodox as a substitute for Doxil, and approving a generic source of preservative-free methotrexate, as well as supporting actions to speed up production of additional supplies of that drug.
“President Obama made it clear that preventing these shortages from happening is a top priority of his administration,” FDA Commissioner Margaret A. Hamburg, M.D. said in a statement. The FDA's actions fall in line with the tenets of President Obama's Executive Order last October to reduce the rising prevalence of prescription drug shortages. The number of shortages had tripled between 2005 and 2010 and had received increasing media attention in recent weeks due to the shortage of methotrexate.
The FDA approved the temporary importation of Lipodox as an alternative for Doxil (liposomal doxorubicin), which is used to treat ovarian cancer after the failure of platinum-based chemotherapy, AIDS-related Kaposi's sarcoma, and multiple myeloma. Lipodox is manufactured at an FDA-inspected facility by Sun Pharma Global FZE in India.
The FDA also prioritized review for and approved a preservative-free generic form of methotrexate, manufactured by APP Pharmaceuticals, a U.S. company. The generic methotrexate supply is available with plans to be in distribution next month, and it will continue to be manufactured indefinitely, according to the FDA news release.
Methotrexate is needed for the intrathecal treatment of children with acute lymphocytic leukemia, and for high-dose therapy of osteosarcoma.
In other steps, the pharmaceutical delivery company Hospira expedited the release of additional supplies of methotrexate to U.S. hospitals and treatment centers—enough to meet a one-month demand. And, the FDA is also working with other drug manufacturers, including Mylan and Sandoz Pharmaceuticals, who have agreed to speed up production to meet the need for methotrexate.
The agency also issued draft guidance to the pharmaceutical industry on detailed requirements for both mandatory and voluntary notifications of drug shortages or supply disruption. The administration's Oct. 31 executive order also supported bipartisan legislation to require prescription drug shortages be reported to the FDA and that would give the agency new authority to enforce those requirements. Early notification of shortages and any discontinuance of supply can have significant, positive impact on addressing the incidence and duration of drug shortages, the FDA noted.