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The picture looks somewhat better than it did a year ago, but many challenges remain.
Drug shortages continue to occur in the United States, but compared to four years ago, the rate has reduced. In addition, the number of drugs in short supply or completely unavailable has declined.
However, the types of products in short supply are as important as drugs used to fight cancer or as ubiquitous as normal saline for IV injection. These shortages can delay care or lead to the use of second-line alternatives that may pose safety and efficacy risks.
In 2011, FDA received reports of 251 drug shortages, of which 183 were for sterile injectable drugs. In 2012, 117 new drug shortages arose, 84 of which were for sterile injectable drugs; however, this number does not reflect the number of drug shortages that had originated earlier and were continuing.
In 2013 and 2014, FDA received fewer reports of new drug shortages (44 for each year), and most shortages occurred among sterile injectables (35 in 2013) and (30 in 2014), according to FDA’s website.
The shortages affect hospitals and health systems nationwide. A national survey of 358 directors of pharmacy conducted in 2013 found that 99% (211 out of 214) reported that they had experienced a shortage of an injectable oncology drug in the previous year. And 64% said that they had completely run out of at least one injectable oncology drug.
Most shortages are due to manufacturing problems, said Erin R. Fox, PharmD, director of the Drug Information Service at University of Utah Health Care in Salt Lake City. If a production line that makes several drugs goes off-line for any reason - contamination problems, machinery breakdown, a natural disaster, a shortage of ingredients -many different products are affected, she said.
Many manufacturers have not retooled their facilities in years, while the number of companies that make a given product may have dropped from three or four to only one, said Allen Vaida, executive vice president of the Institute for Safe Medication Practices (ISMP) in Horsham, Penn. If a sole manufacturer decides to shut down a plant for several months or a year in order to upgrade, or any problems occur, there is a dramatic effect on supplies.
“Shortages are complex and multifaceted, and each shortage situation requires specific evaluation and resolution,” said David Gaugh, RPh, senior vice president, sciences and regulatory affairs, Generic Pharmaceutical Association in Washington, D.C.
Some of the inflexibility in drug manufacturing is due to changing business practices. Manufacturing procedures have been tightened over the last few decades, and both companies and healthcare facilities keep much smaller inventories than they once did, Vaida said, adding, “There is no redundancy in the marketplace.”
In addition, hospitals keep less inventory in stock, Vaida said. Twenty years ago a hospital might receive a wholesale delivery three times a week; now some get deliveries twice a day. One consequence is that low or no inventory means less leeway when a shortage occurs.
Even when the manufacturer comes back up to speed with production, shortages continue for a while. A product may officially be in production, “but no one can buy it for a couple of months because it needs to fill the pipeline back up,” Vaida said.
The FDA angle
The FDA Safety and Innovation Act (FDASIA) of 2012 gave the agency new authority to deal with drug shortages. In 2011, FDA was able to prevent 195 drug shortages; in 2012, 282. In 2013, FDA helped to prevent 170 drug shortages and in 2014, the number of drug shortages averted numbered 101. FDASIA also expanded to 11 the number of FDA staffers dealing with shortage problems, Jensen said.
The act, which includes the Generic Drug User Fee Act, gives FDA authority to collect user fees, which GPhA supports, he noted. Both acts expedite approvals and reduce the backlog of abbreviated new drug applications (ANDAs).
“The only way to mitigate current shortages and prevent future shortages from occurring is a collaborative effort with all stakeholders across the supply chain,” Gaugh said. “This means more communication between regulators and manufacturers, enhancing the ANDA review and approval process, and making sure that generic manufacturers continue to be part of the solution.”
Cancer treatment has been hit hard by shortages of injectable oncology drugs.
“In some cases there is no substitute for the drug in short supply,” said Richard L. Schilsky, MD, chief medical officer of the American Society of Clinical Oncology in Alexandria, Va, last year. “In other cases, there may be a substitute, but it is almost always a brand name, and that increases the cost and out-of-pocket co-pay.”
Shortages of drugs to treat pediatric cancers are especially worrisome, he added.
“You are talking about potentially curative therapy, and you don’t want to jeopardize that.”
Switching drugs can cause other problems. Substituting one drug for another may call for dosing based on body surface area rather than body weight, a change that can cause dosing errors, and the new drug may have a different set of side effects that require different supportive drugs, Schilsky said.
Substitution may mean resorting to a drug that has not been completely tested for the type of cancer it will now be used to treat, Fox said.
Clinical trials in chemotherapy are conducted with very specific combinations of drugs.
“You need to know what to use instead, and nine times out of ten, we don’t know,” she added.
There have been calls for national guidelines on how to cope with oncology drug shortages. Guidelines are needed not only to determine the best substitutions, but also to govern allocation of drugs when they are in short supply.1
ASCO does not keep a list of suitable drug substitutions, Schilsky said. Such a list would be difficult to create, because drug substitutions often depend on the clinical context for a specific patient, he said. However, oncologists know what the potential substitutions would be for a given drug, he added.
Asking doctors to choose which patient will receive a drug in short supply puts them in a very difficult position, Schilsky said. He noted that when he was in practice at the University of Chicago the situation never came to that. “The pharmacist solved the problem in the nick of time, but that puts pressure on the pharmacists and takes more time on their part.”
Pharmacists step up
Because shortages keep recurring, the pharmacy community has learned how to cope. Hospitals have added personnel to monitor the marketplace so that they can react quickly to a shortage when it occurs.
Some of the shortages have repeated themselves, Vaida said. In those instances, pharmacists know what they did the last time to solve the problem.
In the face of drug shortages, pharmacists have scrambled to find scarce supplies of a given product and worked hard to find substitutions or modifications to a drug regimen.
“As healthcare providers, we must take care of the patient. We go to huge lengths with a shortage and do whatever we can,” Fox said. “In some cases, we make this problem invisible.”
Editor's note: This article updates a report published last year.
Valerie DeBenedetteis a medical news writer in Putnam County, N.Y.
• Frequently asked questions about the drug shortages program
Drug shortage databases
• ASHP Drug Shortage Resource Centerhttp://www.ashp.org/menu/DrugShortages
• Current and Resolved Drug Shortages and Discontinuations Reported to FDAhttp://www.accessdata.fda.gov/scripts/drugshortages/default.cfm#A
• FDA’s Drug Shortages Apphttp://www.fda.gov/newsevents/newsroom/pressannouncements/ucm436481.htm