FDA and Industry Collaborating to Prevent Cancer Drug Shortages

Richard L. Schilsky, MD

Shortages of critical drugs—in particular, generic sterile injectables—have posed obstacles to oncologic care over the past decade, but the frequency and severity of shortages have begun to decline through collaborative efforts by the federal government, pharmaceutical industry, patient advocacy groups, and trade organizations such as the American Society of Clinical Oncology (ASCO), experts said during the group’s 48th Annual Meeting.

“The crisis has been particularly bad in cancer care,” said Richard L. Schilsky, MD, professor of medicine and hematology/oncology section chief at the University of Chicago, and chairman of the ASCO Government Relations Committee. “Some of the drugs in shortage are decades old, but irreplaceable. Patient care has been threatened, in many cases. It creates uncertainty, anxiety for patients, and difficulty in planning for physicians.”

Twenty-two cancer therapies have been in short supply over the past two years, according to ASCO President Michael P. Link, MD, professor of pediatric hematology/oncology at the Stanford University School of Medicine, and director of the Bass Center for Cancer and Blood Diseases at the Lucile Salter Packard Children’s Hospital at Stanford.

“In some cases there are workarounds, but for other drugs there really are no replacements available. Without them, we’re faced with the options of delivering suboptimal care and more costly care,” he said.

Michael P. Link, MD

Four months ago, ASCO reported that oncology practices had access to only a two-week supply of preservative-free methotrexate, which has contributed to a “spectacular” 90% cure rate in children with acute lymphoblastic leukemia, the most common form of childhood cancer. While that crisis has been averted, Link said there is now a shortage of sodium bicarbonate, which must be administered along with high-dose infusions of preservative-free methotrexate.

Other drugs in short supply include cisplatin for non-small cell lung and other cancers; Mustargen (Mechlorethamine HCl) for Hodgkin’s lymphoma; paclitaxel for breast and other cancers; and fluorouracil for colon, pancreatic, and other cancers, Link said. Leucovorin, used to modulate the effect of fluorouracil, and irinotecan have also faced recent shortages, said W. Charles Penley, MD, of Tennessee Oncology and incoming chairman of ASCO’s Government Relations Committee.

According to Link, “The problem cuts to the core of every oncologist’s mission, which is to ensure the highest-quality care for every patient. It is most acute in community practices, where the majority of adult patients are cared for. These practices don’t have the pharmacy staff to secure adequate supplies of treatments that are in shortage.”

Link pointed out that ASCO has been working to end the problem by testifying before Congress about potential solutions and, last fall, convening a summit of clinicians, pharmaceutical manufacturers, and the FDA.

Sandra Kweder, MD, deputy director of the Office of New Drugs in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA), agreed that shortages have “affected cancer patients in an extreme way, and also those who need surgery and are having difficulty obtaining the correct anesthetic agents, pain medication, or even antibiotics.” She said the problem “isn’t acceptable,” and that preventing it “is absolutely a priority” for the FDA, Congress, and the federal administration.

Though some experts blame drug shortages on economic issues, Kweder maintained that they primarily have to do with manufacturing problems. Since President Barack Obama’s October 2011 executive order directing the FDA and US Department of Justice to do more to avert drug deficits—in part by encouraging companies to report anticipated shortages—150 shortfalls have been prevented, 50 of them this year, and the number of new shortages has decreased slightly, Kweder said.

She cautioned that, when quality issues such as particles of glass or metal shavings in injectable drugs threaten patients, the FDA may have to temporarily stop production of drugs. She added that the FDA cannot force a company to make a drug.

However, Kweder said that when the FDA is alerted that a shortage is on the horizon due to production difficulties, it can help companies inspect drugs for safety; work with companies—or others that make the same drug—to ramp up their production of a product; and aid companies in importing similar drugs from overseas. To address the doxorubicin injection shortage, she said, the FDA worked with Pfizer to help it relaunch different sterile injectable oncology drugs to be used as substitutes.

The FDA also shares information with the Department of Justice to address the gray market for limited-supply drugs, which involves companies stockpiling the medications and reselling them at exorbitant prices, Kweder said.

“We’re all appalled by that behavior,” Penley said of stockpiling. “It’s no different than profiteering after a major natural disaster.”

Updates to the federal Prescription Drug User Fee Act (PDUFA) will require manufacturers to alert the FDA six months in advance about market withdrawals or drug-supply interruptions, Schilsky said. He added that, under the law, recently passed by both the Senate and the House, the makers of generic drugs will be obligated, for the first time, to pay user fees that will help fund a quicker FDA approval process for new generic drug applications.

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