An intravenous-solution shortage that began in January has left many oncologists and other cancer care providers having to consider alternatives for hydration and chemotherapy preparation—options that have the potential to negatively impact patient care.
Critical shortages of IV solutions, especially sodium chloride solution 0.9 percent, or normal saline, are affecting more than 75 percent of hospitals and other health care settings in the United States, according to a February survey of pharmacy directors who are members of the American Society of Health-System Pharmacists (ASHP). Twenty-one percent of respondents reported that hematology/oncology care was being heavily affected by the shortage.
The shortage is a significant problem for patients and oncologists, agreed Richard L. Schilsky, MD, FASCO, Chief Medical Officer of the American Society of Clinical Oncology. As with the shortage of generic injectables, hospitals without enough IV fluid are often left to their own devices to track down supplies at other facilities, he said.
Ted Okon, Executive Director of the Community Oncology Alliance, noted that he has seen some practices panic. “They're doing the best they can to get saline, but when you have shortages, people want to create an inventory, which creates more shortages because, in essence, you start hoarding,” he said, adding that ultimately, not having enough IV solution puts patient treatment at risk.
The shortage hit critically in early January, and by the middle of the month, the Drug Information Service at the University of Utah in Salt Lake City was receiving reports from hospitals and from within its own system that multiple saline products or particular sizes of products were running out, said Service Director Erin R. Fox, PharmD.
Based on indications from manufacturers about when they may be able to release a full allocation of product, the ASHP estimates that the problem may be resolved by June, said Bona E. Benjamin, BS Pharm, the society's Director of Medication-Use Quality Improvement.
Predicting when the shortage will end is difficult, noted Fox. “We had heard that by end of the first quarter, things would be pretty much resolved and obviously that hasn't happened.” Consequently, suppliers have backed off on stating when the shortage will end. Fox, however, is hopeful that supplies will be back to normal by the third quarter.
Hydrating Patients and Preparing Chemotherapy
Many cancer patients periodically become dehydrated during the course of their illness, “so saline is an important mainstay,” said Schilsky. Depending on their clinical condition, patients may able to take in fluid orally, he noted.
While health care providers at the Ann B. Barshinger Cancer Institute in Lancaster, PA, might have immediately brought in a patient for IV hydration, they now ask themselves whether the individual could be given a half-day to full-day trial of oral hydration, said Randall Oyer, MD, the institute's Medical Director. If this trial isn't effective, then nurses and physicians see if hydration can be achieved with less IV fluid than they normally would use—“We're using what IV fluid we have more efficiently,” he said.
Additionally, the institute's pharmacy staff monitors the FDA drug shortage webpage, tries to skillfully manage the supply chain and puts in strong conservation strategies when necessary, Oyer said. “As a result, the shortage has had a minimal impact on patient care.”
Health care providers at PeaceHealth St. Joseph Cancer Center in Bellingham, WA, have been using Lactated Ringer's and dextrose 5% in water (D5W) solution when possible in lieu of saline for hydration of cancer patients, said Jennie Crews, MD, FACP, the facility's Medical Director and treasurer of the Association of Community Cancer Centers (ACCC).
In addition to hydration, another challenge posed by the shortage is that the majority of chemotherapy products need to be diluted with saline or another solution, said J. Michael Vozniak, PharmD, BCOP, President of the Hematology/Oncology Pharmacy Association (HOPA).
Due to the shortage, pharmacists may recommend to admix medications in a smaller volume of saline or in another solution such as dextrose where appropriate, Vozniak said. Technicians who admix and nurses who administer chemotherapy have to be informed about these changes.
Moreover, most health care settings use computer entry to place medication orders. Shortages may require changes to the order for chemotherapy that is normally admixed in saline. Making these changes can increase the risk for errors, he said.
Some of the chemotherapies that PeaceHealth St. Joseph Cancer Center uses are not compatible with Lactated Ringer's or dextrose, Crews noted. Additionally, certain chemotherapy drugs need to be mixed with saline that comes in DEHP-free bags, which aren't always available. Consequently, pharmacists have to order saline in regular bags, which they then pour into separately ordered empty DEHP-free bags for chemotherapy to be prepared properly, creating extra cost and work, she said.
So far, though, she added, the center has been able to contend with these challenges without delaying patients' cancer treatment.
According to a statement issued by the Food and Drug Administration on January 17, the shortage was caused “by a range of factors including a reported increased demand by hospitals, potentially related to the flu season.” Cumulative influenza-associated hospitalization rates for the 2013–2014 season have surpassed those from three of the last four prior seasons, according to the Centers for Disease Control and Prevention.
However, some remain skeptical about the flu being an explanation for the supply problem. Notably, Okon has talked to many hospitals whose flu patients receive IV saline hydration and administrators there have not been able to corroborate the FDA's claim.
Schilsky said that the cause of the shortages is unknown. However, only three manufacturers—Baxter Healthcare Corp, B.Braun Medical Inc., and Hospira Inc.—make IV saline solution, “so there's not a lot of capacity in the system,” he said. If one or more of them has manufacturing problems, such as particulates in the solution, ramping up production is not easy.
As an example, Baxter International Inc. announced a voluntary recall on December 23, 2013, for one lot of 5% dextrose injection and four lots of 0.9% sodium chloride injection due to particulate matter found in the solutions. How these Baxter recalls might have impacted the supply chain is unknown, Fox said.
FDA and Manufacturer Response
The FDA is working with the three manufacturers of IV solutions as they try to restore supplies to U.S. hospitals and health clinics. Additionally, the agency announced on March 28 that it has approved the import of normal saline to Fresenius Kabi USA, LCC of Lake Zurich, Ill., from its Norway manufacturing facility. However, the shipments will not resolve the shortage, FDA acknowledged.
Baxter was the only manufacturer to comment for this article. The company has seen an increased demand in the U.S. for its IV solutions amid decreased availability of such products from other suppliers, wrote John O'Malley, Baxter spokesperson, in an email to OT. “Baxter has been the one continuous supplier of IV solutions, and the company is making every effort to meet the needs of customers and patients,” he said.
Specifically, Baxter has been manufacturing solutions at maximum capacity in amounts exceeding those of prior years and is making investments to further increase the 2014 supply, O'Malley said. The company is carefully managing inventory through an allocation and fulfillment process to expedite product for urgent need. Additionally, Baxter is working with regulators, customers, clinician associations, and other stakeholders to explore alternative options within the supply chain to alleviate immediate, urgent needs, he said.
According to letters written to their customers in January and posted on FDA's website, Hospira and B.Braun are also trying to meet the increased demand for their IV solution products, which includes addressing their manufacturing processes and inventory management.
Part of a Bigger Problem
Not having enough IV solution, though, is part of a bigger supply problem in oncology—namely a shortage of generic sterile injectables, which began to escalate in 2008 and 2009, Okon noted. While the FDA tried to remedy the situation, its approach was a “Band-Aid,” rather than a long-term solution, he said. “The supply problems keep resurfacing with chemotherapies, supportive care, and now with IV saline.”
Drug shortages are essentially an economic problem, Okon continued. The Medicare Prescription Drug and Modernization Act of 2003 changed reimbursement for part B drugs, which are administered in physician offices or the outpatient setting.
“The aim was to cap pricing increases on brand drugs, but the act also took the floor out from under the pricing of generic drugs,” he said. Extremely low-priced generics caused the manufacturing base to dry up on injectables, he said.
Moreover, Medicaid rebates and discounts from the 340B Drug Discount Program have continued to eat into profits. Consequently, manufacturers don't have the revenue to invest in new plants and equipment, adding to production and quality problems of their products, he said.
Any long-term solution will require a thoughtful analysis of the economic business model of generic drug production, said Schilsky.
In the meantime, all stakeholders need to work together to help mitigate future shortages, Vozniak noted. “Transparency and communication that a shortage is coming allow health care providers to prepare.”