Drug shortages challenge the healthcare community, FDA, and pharmaceutical manufacturers

Key Points

The outcry from physicians, pharmacists, and patients over disruptions in supplies of vital medicines to treat cancer, pain, and other serious conditions is drawing attention from the White House, Congress, and the broader healthcare system. Oncologists can't obtain widely-used chemotherapies to treat seriously ill patients. Surgeons are postponing operations because they lack key anesthetics and pain medications. Doctors are struggling to obtain vital parenterals for premature babies and for patients requiring infusion. And dozens of clinical trials have been halted because investigators lack adequate supplies of cancer drugs used as components of treatment arms or as controls.

While there always have been periodic drug shortages, the problem has become much more acute in the last 2 years. The main culprit appears to be drug manufacturing and supply chain failings, particularly related to generic sterile injectables. Decisions by firms to exit certain low-profit markets often leave only 1 or 2 producers for critical therapies. Some observers charge that too-strict oversight by FDA aggravates the problem-while others blame industry negligence and business practices that put the public health at risk. Another possibility is that policies and practices that drive down reimbursement for old-line generics discourages industry investment in low-profit therapeutic categories that are difficult to produce.

These issues made headlines as President Obama issued an Executive Order Oct. 31, 2011, directing FDA to enforce reporting requirements for manufacturers facing short supplies of critical drugs and to facilitate production of alternative medicines. The administration's actions followed hearings in September on the drug shortage crisis and broader pharma supply chain problems. An FDA public workshop held on September 26 also provided a forum for health professionals, patient advocates, drug distributors, and manufacturers to air concerns and propose remedies for short drug supplies. The resulting publicity has boosted interest in legislation to address pharma supply chain issues in general, and drug shortages in particular. FDA also issued a report analyzing steps it can take to tackle shortages within its current limited authority, and the Government Accountability Office is examining the causes and responses to the supply crisis.

FDA recorded 178 drug shortages in the United States in 2010, up from 157 in 2009-and much more than the 50 to 60 range of previous years, reported Edward Cox, coordinator of the drug shortage program in the Center for Drug Evaluation and Research (CDER), to open the FDA workshop. The University of Utah Drug Information Service recorded 210 shortages this year as of mid-September, and is tracking some 260 active shortages.

Shortages in parenterals have taken a toll on hospitals and clinics: a survey by the American Hospital Association in June found that virtually all hospitals have experienced at least 1 drug shortage this year, and half report 21 or more supply problems. This builds on a March 2011 survey by the Premiere Healthcare Alliance that documented soaring shortages along with exorbitant prices for these products.

Three-fourths of the shortages reported to FDA last year involved sterile injectables-and almost all of them for "medically necessary" drugs, noted Howard Koh, MD, assistant secretary for health in the Department of Health and Human Services (HHS), at a hearing before the House Energy and Commerce Health subcommittee. Dr Koh cited a long list of underlying factors driving the short supply trend: industry consolidation, limited raw materials, changes to inventory and distribution practices, production delays, increases in demand, and business decisions to close a manufacturing site or discontinue production. When there are only 1 or 2 sources for a critical drug, small shift in production lines, plus just-in-time inventory controls at hospitals, make it hard to buffer the impact, explained pharmacist Richard Paoletti of Lancaster General Health, Lancaster, Pa.