Drug shortages have become much more acute in the last two years, largely due to manufacturing failures and supply chain disruptions
involving critical treatments. 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.
These issues made headlines as Congressional committees held hearings in September on the drug shortage crisis and broader
supply chain problems. An FDA public workshop also provided a forum for health professionals, patient advocates, drug distributors,
and manufacturers to air concerns and propose remedies. The resulting publicity has boosted support on Capitol Hill for legislation
that addresses pharma supply chain issues in general, and the drug shortage situation in particular. FDA has prepared a report
analyzing steps it can take to tackle shortages with its current limited authority, and the Government Accountability Office
(GAO) is examining the causes of and responses to the drug shortage crisis.
FDA recorded 178 drug shortages in the US 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 at the Center for Drug Evaluation and Research (CDER),
at the FDA workshop. The University of Utah Drug Information Service identified 210 shortages for drugs and biologics as of
mid-September and is tracking some 260 active shortages nationwide.
Prices Too Low?
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, assistant secretary for health in the Department of Health and Human Services (HHS), at
a hearing before the House Energy and Commerce health subcommittee. Koh cited a long list of underlying factors: industry
consolidation, lack of raw materials, changing inventory and distribution practices, production delays, rising demand, and
business decisions to close down plants or exit low-profit markets.
One popular remedy is for manufacturers to inform FDA in advance of supply problems. The agency reports that early warnings
helped it head off 38 potential shortages in 2010 and 99 so far this year. When FDA knows of a looming supply interruption,
its staff can expedite the approval of new suppliers, alternative production sites, and changes in product specifications.
Agency officials also can bend the rules to keep a violative product on the market, to encourage other firms to ramp up production,
and to permit temporary importation of unapproved products to fill supply gaps.
FDA officials emphasize their regulatory flexibility to counter charges that overly aggressive enforcement of manufacturing
rules aggravates supply problems. The agency doesn't halt production for minor violations, they insist, but only for significant
problems with drug sterility and contamination. Before requesting a drug recall or seizure, they check to make sure such action
won't precipitate a shortage. However, FDA enforcers will take action when they find glass and metal particles in vials and
new impurities and degradants.
Under current law, FDA often lacks information on looming shortages because only sole-source manufacturers of critical medicines
have to give notice of plans to discontinue production. Some companies voluntarily inform FDA of likely short supplies, but
most do not, and often such information comes in too late for timely action.
To remedy this limitation, Congress is considering legislation requiring six-months advance notification of production changes
for a broad range of prescription drugs. There would be penalties for noncompliance, along with leeway for companies able
to demonstrate that a problem could not be anticipated.
While advance notification may help FDA head off some shortages, the danger is that early release of information on production
problems could lead to hoarding and price gouging. Hospitals and doctors report that gray market profiteers are inundating
them with faxes and phone calls offering scarce drugs at huge markups. In response, Rep. Elijah Cummings of Maryland, the
top Democrat on the House Oversight and Government Reform Committee, launched an investigation last month of leading secondary
distributors, seeking information on sources and profits on certain drugs.
And advance notification is not always possible. FDA officials concede that many manufacturing problems cannot be anticipated,
such as equipment breakdowns, plant fires, and natural disasters such as earthquakes and volcanoes that can disrupt supplies