Drug shortages appear to have eased somewhat from last year’s crisis, thanks to federal regulatory interventions early this year. By the end of last month, 123 new drug shortages had been reported for 2012, compared to 211 new shortages for the same period in 2011.
But the underlying factors responsible for last year’s crisis are far from resolved, and shortages can be expected to persist well into the future, according to the FDA’s deputy director for new drugs, Sandra Kwender, who has predicted it will be “several years before companies building new plants get them up and running.”
Following an executive order by President Obama in February, the FDA issued new guidelines for industry’s voluntary reporting of impending disruptions in manufacturing. In a few cases, the FDA also temporarily and partially lifted pharmaceutical import restrictions, allowing importation of Lipodox as a substitute for Doxil, for example.
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Shortages for Propofol, morphine, Valium, and other pain medications and sedatives – some of which are important in pain management and palliative care for cancer patients – endure, in some cases prompting emergency medicine personnel to rely on expired drug lots.
Oncology and anesthesiology drugs have been most seriously affected by shortages in recent years, according to the FDA, which has documented shortages of 20 sterile injectable chemotherapy drugs. In addition to Doxil, shortages have involved paclitaxel, cisplatin, leucovorin, etoposide, fluorouracil, and preservative-free methotrexate. (Supplies of the radioisotope technetium-99m also dropped after aging nuclear reactors producing it and molybdenum-99 were taken off-line for repairs in 2009 and 2010.)
In New York City, one hospital reported in June 2012 that drug shortages in 2011 had caused documented changes in treatment plans for nearly 10% of cancer patients. ChemotherapyAdvisor reported that cancer drug shortages at this hospital involved 12 medications in 2010, but 22 by 2011. Even when substitute drugs exist, toxicities and efficacy can vary, and conversion factors may not be well understood.
The causes of these shortages have ranged from planned manufacturing facility upgrades, regulatory actions, and increased demand (including stockpiling by desperate hospitals and clinics), to production problems for bulk source materials and consolidation of generic drug manufacturing. Many shortages have involved standard chemotherapies that are no longer on patent. But because there is precious little manufacturing redundancy in production of generic drugs, halts in production at a single manufacturing facility can disrupt much of the world supply of a crucially-important medication.
The FDA views shortages as a reflection of insufficient production capacity and aging manufacturing infrastructure. But the congressional House Oversight Committee largely – and controversially — blamed regulators at the FDA themselves for drug shortages, citing enforcement actions that “effectively shut down 30% of the total manufacturing capacity at four of America’s largest producers of generic injectable medications.” Doxil supplies were disrupted last year, for example, after repeated quality-control lapses identified during FDA inspections of a manufacturing plant in Ohio, and resulting recalls of other drugs produced at that facility.
In July, President Obama signed into law the 2012 FDA Safety and Innovation Act (FDASIA), which includes new statutory reporting requirements for drug manufacturers to notify the government at least 6 months ahead of time when planning to discontinue production of a medication. The new law broadens the FDA’s authority to inspect drug and bulk drug-ingredient manufacturing facilities in China, India and other countries, and streamlines clinical trial requirements for new drug approvals.
FDASIA also increases penalties for counterfeit drug manufacturing and distribution – a problem that has grown in lock-step with drug shortages over recent years, highlighting the dangers of purchasing critical drugs on the gray market, where chain of custody documentation is scant, suspect, or absent. Counterfeiters now face up to $4 million in fines and 20 years in federal prison, up from the previous maximum penalties of $10,000 and 3 years in prison.
FDASIA places the United States at the forefront of the effort to monitor and curb drug shortages, but experts describe it as a stopgap or first step, rather than a final remedy.
“The enactment of this law makes significant strides in addressing a crisis in public health,” said ASCO’s immediate past president, Michael Link, MD. “But our work is not done.”
ASCO advocates enforcement provisions, including strict penalties for manufacturers who do not comply with the law.
In June, the American Society for Hematology (ASH), European Hematology Association, and European Cancer Patient Coalition joined forces to track and report international shortages in standard chemotherapy drugs.
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