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Partially in response to recent shortages of such critically needed cancer drugs as doxorubicin hydrochloride liposomal injection (Doxil) and methotrexate, the FDA has issued draft guidance on detailed requirements for both mandatory and voluntary notifications to the agency of issues that could result in a drug shortage or supply disruption of a prescription drug or biological product. 


On October 31, 2011, the FDA sent a letter to manufacturers to raise awareness of the importance of early notification of drug shortages or supply disruptions. According to the agency, the annual number of such shortages tripled from 61 in 2005 to 178 in 2010. Of particular concern were medications that are manufactured by a small number of firms and for which no good substitutes exist. 


To address the recent Doxil shortage, the FDA approved temporary importation of another doxorubicin hydrochloride liposomal injection. The agency handled the methotrexate shortage in part by expediting review of the application for a preservative-free formulation of the agent. 


Under current regulations, the sole manufacturer of a drug that is deemed life-supporting, life-sustaining, or intended for use in the prevention of a debilitating disease or condition is required to notify the FDA at least 6 months prior to discontinuing manufacture of the product in question. However, in 2010, only 8% of drug shortages were attributable to permanent discontinuances of the product: The majority of shortages resulted from problems at the manufacturing facility, delays in manufacturing or shipping, and shortages in active pharmaceutical ingredients. In addition, some biological products are vulnerable to shortages but are not subject to mandatory reporting. Under current law manufacturers are not required to report to the FDA the majority of situations that could lead to a drug shortage, and the agency has begun strongly encouraging companies to voluntarily report any issues that could lead to a shortage of any prescription drug or biological product supplied in the United States.


Approximately 4 months after sending the awareness-raising letter to manufacturers, the FDA registered a sixfold increase in voluntary notification by industry of potential shortages, and distributed a draft guidance for industry on requirements for notifying the agency of a discontinuation of certain drug products (Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product Shortage). 


Whereas all permanent discontinuances of production must continue to be reported to the FDA, the agency is now also asking for even temporary interruptions to be reported if the interruption can reasonably be expected to lead to a disruption in supply of the product. In the draft guidance, the FDA urges manufacturers to be over-inclusive when determining whether the product is life-supporting, life-sustaining, or is used for a debilitating disease or condition, and to be similarly liberal when determining whether they are a sole manufacturer. But the agency is encouraging notification even when companies are not the sole manufacturer of a drug or biological product, and is encouraging voluntary notification for all prescription drug and biological products.


Comments and suggestions regarding this draft document should be submitted to the FDA by May 29, 2012. (Submission information is included in the document.) ■