No Band-Aid Solution to Nation’s Drug Shortage

The prompt action by the FDA and generic drug manufacturers to a recent shortage of cancer drugs served as a quick fix for patients, but experts say more needs to be done to find a permanent solution.

The shortages of sterile injectable products like preservative-free methotrexate and doxorubicin liposomal injection in February are just the latest additions to the FDA’s ever-expanding drug-shortage list.

In 2010 there were 178 drugs on the shortage list; by 2011, the number had expanded to 220, according to Captain Valerie Jensen, associate director of the Drug Shortage Program, Center for Drug Evaluation and Research, FDA. As of last month, there were 238 prescription drugs in short supply or unavailable nationwide.

Dr. Peter Adamson, chair of the Children’s Oncology Group says the drug shortage list currently includes eight life-saving cancer drugs that don’t have any effective substitutes.

Drugs currently on the list have revolutionized the cure for testicular cancer and help treat breast and ovarian cancer.

What’s worse, the shortage puts sick children at high risk. “In pediatrics, 80% of these regimens are curative, claims Dr. Michael Link, president of the American Society of Clinical Oncology. “Since the 1960s, we took [acute lymphoblastic leukemia] that was uniformly fatal and now we have a cure in about 90% of childhood cases.”

The shortage also affects clinical trials, says Dr. Donald Harvey, director, phase 1 clinical trials program at Winship Cancer Institute of Emory University. Pipeline drugs are often added to the existing backbone of a clinical trial. A shortage of even one drug requires the trial to be put on hold, curbing potential innovations and breakthroughs.

Wrong tools cause real-time scurrying

To alleviate the drug shortage in February, the federal regulators approved new suppliers for two crucial cancer drugs, but Adamson argues the FDA does not have the ability or the right tools to tackle shortages proactively or prioritize drugs for which there are no good alternatives.

Last month’s shortage was not unexpected. In November, generic drug manufacturer Ben Venue Laboratories, which produces doxil, closed a facility because of the compromised quality in safety and effectiveness of some of its products.

The shutdown forced regulators to scurry to find adequate alternatives including the fast-tracked approval of an application from generic manufacturer APP that committed to marketing a preservative-free formulation of methotrexate in late March or early April. The agency also temporarily allowed shipments from India of the drug Lipodox, an alternative to Doxil, the brand name for doxorubicin.

While the FDA’s actions were lauded in the health community, the scenario highlights certain systemic failings: the communications blip between FDA and generic manufacturers and among generic drug makers themselves.

Plant problems

In the U.S., the lion’s share of the sterile injectable oncology market is generic and rising, according to Ralph Neas, president and CEO of the Generic Pharmaceutical Association. About six or seven manufacturers make 90% of generic sterile injectables, which require a complex rule-and-regulation manufacturing set.

The manufacturing lines at each generic facility operate in runs that may last hours or weeks. Things will inevitably go wrong and manufacturers may encounter a situation in which they are unable to keep a plant running.

The objective is to get capacity on-line and have plants meet good manufacturing standards.

In October, President Obama issued an executive order addressing the drug shortage. FDA ‘s recent “Guidance for Industry” is a nonbinding recommendation that mandates sole manufacturers of life-saving drugs to notify FDA six months before discontinuance of product. The guidance also encourages voluntary reporting of all shortages.

Notification is an important first step, says Adamson. “While it doesn’t solve the problem, it at least sets the stage for more rational approaches and less crisis mentality.”

Since institution of the voluntary requirement, notifications have grown from 10 to 60 per month, Jensen says.

Similarly, the Accelerated Recovery Initiative (ARI) proposed by GPhA and funded by generic manufacturers calls for the creation of a multistakeholder initiative and voluntary communication between an independent third party and stakeholders involved in the manufacturing and distribution of generic injectable medications in shortage, as well as an FDA SWAT team to respond quickly to drug shortages.

ASCO supports the Preserving Access to Life-Saving Medications Act and the Drug Shortage Prevention Act introduced in Congress.

ASCO’s recently-published recommendations go even further than the bills and request Congress to establish FDA user-fees for generic drugs and provide economic incentives for companies to develop contingency plans that ensure continued drug availability.