Hospitals scramble on the front lines of drug shortages
By Lena H. Sun,
The situation was urgent. The operating room and many key units at MedStar Washington Hospital Center were running low on a critical anesthetic. Suppliers were out of the most commonly used dosages. The only remedy was for pharmacy staffers to dilute a higher concentration with saline solution to produce the needed strength.
Ann Breakenridge, an assistant pharmacy director, needed action immediately. “We have an acute shortage situation,” she told Renee McCarthy, who oversees the lab. “I need somebody to make some midazolam syringes, like yesterday.”
On that recent Tuesday, technicians filled 400 syringes with the anesthetic, enough to last an additional two or three days. The painstaking process took more than four hours.
“And it’s just one drug,” Breakenridge said. “You sit there and you’re like, ‘Wow.’ ”
Shortages of prescription drugs have been a growing concern for the past six years. They nearly tripled from 2005 to 2010 and reached record levels in 2011 as manufacturers ceased operations or ran into production problems. The Food and Drug Administration has been scrambling to respond, helping firms resume production more quickly and approving emergency imports of supplies. Recent approvals of new suppliers helped ease shortages of two crucial cancer drugs.
In some cases, lifesaving treatments have been delayed, sending patients on desperate searches for needed medicines, doctors say. Shortages have also caused injuries from mistakes and at least 15 deaths around the country since mid-2011, according to the Institute for Safe Medication Practices, a nonprofit that tracks medication errors. The mistakes included confusion about dosing and preparation of substitutes.
Shortfalls are so common that pharmacy staffers at hospitals are spending many extra hours to ensure an uninterrupted flow of medicine to cancer patients, victims of heart attacks and accidents, and a host of other ill people.
“It’s very, very time-consuming, and it involves a lot of people,” Breakenridge said, referring to the multiple steps needed to manage each shortage. “It impacts operations tremendously. And it’s just to try to make sure that the patient comes in and everything is seamless for them.”
More than 210 drugs are in short supply or totally unavailable, according to Bona Benjamin of the American Society of Health-System Pharmacists. The majority are generic injectable medications widely used in hospitals, including drugs used to relieve pain, fight cancer or infections, anesthetize surgical patients, treat cardiovascular disease, and manage psychiatric conditions.
Critical intravenous nutritional supplements and drugs for controlling attention-deficit hyperactivity disorder are also hard to find, according to the pharmacists group.
Most hospitals rarely get advance notice of the shortages, explanations of what caused them or estimates of how long they will last. So pharmacists scramble. They repackage higher concentrations into smaller doses. They find substitutes, which can often be more expensive. They ration drugs.
Pharmacists spend an average of eight to nine hours a week addressing drug shortages, compared with three hours a week in 2004, according to an industry estimate.
Last year, nearly half of hospitals reported experiencing a drug shortage on a daily basis, according to a survey of 820 hospitals by the American Hospital Association. About 82 percent of hospitals said they delayed treatment because of a shortage, and 35 percent of hospitals said patients experienced “adverse outcomes.” The survey did not categorize those outcomes, a spokeswoman said.
Washington Hospital Center’s pharmacy director, Jay Barbaccia, said the recent scarcity of cancer drugs has delayed treatment for some patients. But he is not aware of errors or other harm to patients caused by the shortages.
“We may be more aggressive and facile in dealing with these shortages,” he said. “We jump on these things immediately. We don’t wait.”
Juggling supplies and needs
Like its counterparts at many hospitals, Barbaccia’s team has a daily morning huddle to discuss operational issues, and drug shortages have become a standard topic. The hospital tries to keep a five-day supply of drugs. If there is a new shortage of a drug, pharmacists need to quickly calculate which departments use it, how much they use and how long existing stock will last. Affected doctors and nurses must be notified.
When injectable vitamin K was scarce and another delivery was not expected for a week, the hospital chose to give it only to newborns, Barbaccia said. Newborns have no alternative medication, he said, and a limited supply can treat “a whole bunch of babies.” Adults who would normally receive it to stem bleeding could use another medicine, Factor VII — which costs $6,000 a dose, compared with $18 a dose for injectable vitamin K.
In the end, more vitamin K arrived, so the expensive drug wasn’t used, Barbaccia said.
Sometimes, even substitutes are scarce.
After the FDA recently allowed the temporary importation of Lipodoxto treat ovarian and other cancers because of a shortage of Doxil, clinicians hoped that there would be enough to allow cancer treatments to continue. But Washington Hospital Center could obtain only 23 vials of Lipodox, enough for two patients to have two courses of treatment, even though there were 12 eligible patients, said Laura Wolverton, the pharmacist at the hospital’s Cancer Institute. The patients are receiving their injections on the same day to make the most effective use of each vial, Wolverton said.
A handful of remaining patients are receiving other chemotherapy drugs or are on a waiting list for Doxil, she said.
Often, hospitals resort to mixing drugs for their own use, which they are allowed to do. Doing so maximizes supplies and minimizes the chances of error, pharmacists said.
While the midazolam preparations were underway that recent Tuesday, pharmacists discovered another shortage. Standard doses of lorazepam, an anti-anxiety medication, had not arrived in the morning’s delivery. Luckily, the hospital had the proper strength in a larger-size bottle. So technicians on the evening shift were assigned to fill 200 syringes with individual doses.
The shortages often mean overtime for technicians and longer hours and more juggling for pharmacists.
“The scary part is that it’s always the common drugs that you use every day — those are the ones that are disappearing off the market,” said McCarthy, the lab manager.
Why the shortages?
A number of complex factors are contributing to the shortage, experts said.
Many of the drugs in short supply, particularly older generic ones, are “sterile injectable” medications that are more complicated to produce and more prone to manufacturing problems.
Sometimes these older drugs are discontinued in favor of newer, more profitable drugs, officials said.
That leaves only a handful of sources for the drugs. More than 50 percent of the drugs on the FDA’s shortage list are supplied by three or fewer manufacturers, industry and government officials said. If one facility has production problems, cannot obtain ingredients or fails an inspection, other companies cannot ramp up production quickly.
Quality problems, including fungal contamination and findings of glass shards and metal filings in drugs, were the leading cause of drug shortages, according to an FDA report in October.
The shutdown of four factories by an Ohio lab because of serious quality problems contributed to the cancer-drug shortages. Although those have eased somewhat because of new suppliers, the idled factories are a big reason for the scarcity of other drugs, said Valerie Jensen, associate director of the FDA’s drug-shortage program.
“Right now, anesthesia is a big concern,” she said. “These drugs are absolutely in critical shortage.”
Federal regulators are speeding the application process for a few new firms seeking permission to make these older drugs, and manufacturers are providing earlier notification of potential shortages, she said. Federal officials say 195 drug shortages were prevented in 2011, 114 of them after President Obama issued an executive order in October telling regulators to ramp up efforts.
The number of new shortages so far in 2012 is half of what it was for the same period last year, about 30 compared with more than 60, said Erin Fox of the University of Utah, who monitors drug shortages for the pharmacists group.
“On the other hand, it doesn’t make a difference if the rate of new shortages is falling when you’re dealing with the shortage that is impacting your patients right now,” she said.
Bipartisan legislation pending in Congress would require drug companies to notify the FDA of potential shortages far earlier than is mandated under current federal law. The generic-drug industry is also agreeing to provide the FDA with nearly $300 million in user fees to speed drug applications, similar to the system in place for brand-name drugs.
For the longer term, the generic-drug industry is proposing that an independent third party act as a clearinghouse between drugmakers and the FDA. Right now, if the FDA knows Company A has a potential shortage, the agency cannot, for proprietary reasons, tell companies B and C how much more to make. That makes it difficult for companies, which are already at capacity, to know how much more is needed, said Ralph G. Neas, who heads the Generic Pharmaceutical Association.
If the proposal is accepted by the Federal Trade Commission and the Department of Health and Human Services, industry officials say the clearinghouse could launch by mid-April. It would still be months before companies add production.
‘That’s precious gold’
Washington Hospital Center installed a metal door two years ago to better guard drugs that are in short supply. Only a few people have access to the key. Breakenridge is one of them.
Working with the hospital’s chief drug buyer, Rakesh Khandelwal, she helps manage the response. Khandelwal is often the first to hear about shortages. He tries to calculate how long a shortage might last, and the hospital tries to buy protectively.
“And we jump on it and we order, but everybody else is out there doing the same thing,” Breakenridge said.
Back in the lab, technician Joe Siderowicz, in protective scrubs, cap and bootees, is starting the dilution. Along the way, a label-maker breaks after cranking out 400 labels, one by one. Labeling is the most tedious part of the job. Labels can’t cover up syringe marks; they can’t be creased on the bar code. “You have to be very precise,” Siderowicz said.
Inside the “clean room,” he uses a large syringe to pull out the vials’ contents before mixing them with saline. He swabs each vial with an alcohol wipe, then draws out 10 milliliters from each vial. He does this 16 times.
When he’s done, one vial remains intact. Manufacturers had overfilled the other bottles, so he had what he needed. He set the vial aside.
“We have one left over,” said lab manager Renee McCarthy. “That’s precious gold right there.”