Robin Miller, a 62-year-old oncologist in Atlanta with bladder cancer, was scheduled to receive a potentially lifesaving drug in December. But her doctor’s office called shortly before the appointment to say: “Sorry, we don’t have any. We can’t give it to you,” according to Dr. Miller.
The disruption was due to a global shortage of the drug, BCG, which arose after manufacturing problems at two of the few global suppliers. Without the drug, Dr. Miller feared her cancer would come back and she would have to have her bladder removed, a step she called “barbaric.”
The BCG shortage followed a 2012 mold infestation that halted production for more than two years at an aging factory in Toronto owned by France’s Sanofi SA. The drug’s only other manufacturer for the U.S., Merck & Co., has recently suffered production delays of its own.
Some of the thousands of patients who depend on BCG have resorted to tracking online message boards, calling hospitals and traveling hundreds of miles to find supplies. Some patients have gone without BCG while others have received less effective alternatives. “There are patients who aren’t getting optimal therapy right now,” says Dr. Edward M. Messing, a urologist at the University of Rochester Medical Center in Rochester, N.Y.
The crisis illustrates the potentially grave consequences of a persistent problem in health care: drug shortages. The number of drugs in short supply in the U.S. has risen 74% from five years ago, to about 265, according to the University of Utah’s Drug Information Service, which tracks supplies. They range from antibiotics and cancer treatments to commodity items such as saline.
Interviews with company executives, hospital pharmacists and regulators point to several causes of the shortages. Companies have failed to build enough production capacity, haven’t maintained equipment, and failed to ward off contamination in aging plants. A U.S. Food and Drug Administration crackdown on shoddy quality unintentionally worsened the shortages because some companies responded by shutting down plants or scaling back production during renovations.
Many of the scarce drugs are older, injectable treatments that can be complex and costly to manufacture, but which command relatively low prices because they aren’t protected by patent. Hospitals and doctors’ offices are the main buyers of the drugs. Companies can’t easily increase prices because insurers reimburse many generic hospital-administered drugs under a payment system that is more frugal than for other medicines.
Among the current shortages is the generic painkiller ketorolac, widely used in hospitals during and after certain surgical procedures. Hospira Inc. of Lake Forest, Ill., a major U.S. manufacturer of the drug, notified customers in January it was recalling more than 18 million vials because of contamination by crystal particles. The company said it has taken corrective action and resumed shipping most versions of the drug.
“The shortage of ketorolac deeply affects patient care, as we don’t have great substitutes,” says Sean Adams, an anesthesiologist in Naperville, Ill. “The staff time and expense of managing shortages is enormous. Worse, there are significant patient risks with shortages,” including more side effects with alternative drugs.
The antibiotic Zosyn and its generic equivalents, used to treat infections including pneumonia, also are in short supply. Pfizer Inc., which makes Zosyn, said an increase in global demand and “unplanned” maintenance and repairs at a plant in Italy had caused the shortage. It expects to resume shipping vials in September.
Barbara Murray, director of the division of infectious diseases at University of Texas Medical School in Houston, said the shortage sometimes forces doctors to switch to less effective alternatives.
Hospital emergency rooms have grappled with various shortages. Daniel Miller, an associate professor of emergency medicine at the University of Iowa Carver College of Medicine, says he has been unable to get a supply of droperidol, a drug commonly used in the emergency room to relieve migraine headaches, abdominal pain and nausea. Alternatives such as narcotics are less effective, he says. Manufacturers have reported production delays and raw-material shortages, according to the Drug Information Service.
Sanofi resumed production of the bladder-cancer drug BCG in Toronto last fall, but shipments aren’t expected until later this year. Merck has more than doubled production of its BCG product at a plant in North Carolina, but last summer the company detected a possible air-quality problem and suspended production for six weeks, causing shipment backlogs that persist. The FDA says BCG’s few foreign suppliers haven’t been in a position to quickly boost production.
BCG, a liquid delivered into a patient’s bladder, is expensive to manufacture because it is derived from live bacteria. Yet because the therapy is 25 years old and no longer protected by patent, it fetches only about $145 a vial, compared with about $2,700 for a vial of Avastin, a newer, patented drug for other forms of cancer that hasn’t had shortage issues.
RAMSAY DE GIVE FOR THE WALL STREET JOURNAL Mary Greene of New York experienced a delay in treatment for bladder cancer last year because the drug BCG was in short supply.
BCG’s low price, coupled with the complexity and cost of manufacturing, has made the drug unattractive for many companies to produce, says Erin Fox, director of the drug information service at the University of Utah.
