"A drug shortage can be a frightening prospect for patients and President Obama made it clear that preventing these shortages from happening is a top priority of his administration," said FDA Commissioner Margaret A. Hamburg, M.D. "Through the collaborative work of FDA, industry, and other stakeholders, patients and families waiting for these products or anxious about their availability should now be able to get the medication they need."
In response to the critical shortage of the cancer drug Doxil (doxorubicin hydrochloride liposome injection) and rapidly declining supplies of methotrexate, the FDA took proactive steps needed to increase available supply for patients in the U.S. For Doxil, there will be temporary importation of a replacement drug, Lipodox (doxorubicin hydrochloride liposome injection), which is expected to end the shortage and fully meet patient needs in the coming weeks. For methotrexate, in addition to already announced actions, the Agency has approved a new manufacturer of preservative-free formulation of methotrexate that is expected to further bolster supply and help avert a shortage of this lifesaving medicine. FDA expedited review of the application to help address this potential shortage.
In addition, in response to President Obama's Executive Order on prescription drug shortages, FDA today issued draft guidance to industry on detailed requirements for both mandatory and voluntary notifications to the agency of issues that could result in a drug shortage or supply disruption. Increased awareness of the importance of early notification due to President Obama's Oct. 31, 2011, Executive Order and FDA's letter to manufacturers on the same day has resulted in a sixfold increase in voluntary notifications by industry of potential shortages. In 2011, there were a total of 195 drug shortages prevented. Since the Executive Order, FDA has prevented 114 drug shortages.
Under FDA's exercise of enforcement discretion the chemotherapeutic drug Lipodox will be imported as an alternative to Doxil. Doxil is used in multiple treatment regimens, including treatment of ovarian cancer after failure of platinum-based chemotherapy. The drug is also indicated for use in AIDS-related Kaposi's sarcoma and multiple myeloma. FDA anticipates that the incoming supply of Lipodox will be able to fully meet patient needs.
FDA's exercise of enforcement discretion for Lipodox is a temporary, limited arrangement specific to Sun Pharma Global FZE and its authorized distributor, Caraco Pharmaceutical Laboratories Ltd.
Temporary importation of unapproved foreign drugs is considered in rare cases when there is a shortage of an approved drug that is critical to patients and the shortage cannot be resolved in a timely fashion with FDA-approved drugs.
When a company is identified that is willing and able to import the needed drug product, FDA evaluates the foreign-approved drug to ensure that it is of adequate quality and that the drug does not pose significant risks for US patients. Only after successful evaluation of these factors does FDA exercise its enforcement discretion for the temporary importation of an overseas drug into the U.S. market.
With regard to methotrexate, a drug that is needed for the treatment of many forms of cancer and other serious diseases, FDA has successfully engaged many firms to assist in maintaining supplies to meet all patient needs. Preservative-free methotrexate is needed for the intrathecal (injection into the fluid surrounding the brain and spinal cord) treatment of children with acute lymphocytic leukemia (ALL) and for the high-dose therapy of osteosarcoma.
First, FDA has prioritized review of and approved a preservative-free methotrexate generic drug manufactured by APP Pharmaceuticals and expects that product to become available in March and continue indefinitely. Second, Hospira expedited release of additional supplies, resulting in 31,000 vials of new product - enough for more than one month's worth of demand - being shipped to hundreds of U.S. hospitals and treatment centers today. FDA is actively working with other manufacturers of methotrexate who have also stepped up to increase production in order to meet patient needs, including Mylan and Sandoz Pharmaceuticals.
APP's application for preservative-free methotrexate is a supplement to its already approved generic drug application that the firm had previously discontinued. When FDA became aware of potential problems with the supply of the drug (due to the largest manufacturer, Bedford/Ben Venue voluntarily closing its plant), the Agency reached out to other firms to see how FDA could assist to meet the shortfall.
Prior to approval of APP's application and subsequent to Ben Venue's voluntary shutdown, FDA worked with Ben Venue on release of already manufactured preservative-free methotrexate, following confirmation of its safety. This supply is available already and will provide emergency supplies as the other firms also work to increase production of methotrexate in response to requests by FDA and the public.