Long-term solutions sought for shortages of vital oncology drugs

Issue: July 10, 2012

An unprecedented number of shortages of critical and relatively inexpensive generic injectable oncology drugs continue to cause tremendous uncertainty for patients with cancer, according to several physicians who participated in a panel discussion during the 2012 ASCO Annual Meeting.

Supplies of 22 oncology drugs have run low in the past 2 years, according to Michael P. Link, MD, ASCO’s immediate past president and service chief of pediatric hematology-oncology at Lucile Packard Children’s Hospital at Stanford in Palo Alto, Calif.

Michael P. Link

In some cases, physicians find workarounds or substitutes that still benefited their patients. In cases in which alternatives were not available, physicians are forced to choose less-than-optimal therapy or deliver more costly care.

“Looking at current drug shortages, the most essential mainstays of modern cancer therapy for both adults and children are in short supply,” Link said. “In some cases, we temporarily addressed the threat to patient care, as one or two manufacturers stepped up production. But other companies are still reporting problems, and the long-term availability of these vital medicines remains uncertain. We are seeking long-term solutions to ensure that the shortages are no longer a threat to patient care.”

Although the frequency of shortages has declined slightly, the unpredictable availability of certain generic drugs can make it difficult for physicians to properly plan a treatment course for their patients. In February, for example, many oncology practices were down to a 2-week supply of preservative-free methotrexate, a critical treatment for children with acute myeloblastic leukemia.

“This had an enormous impact on a disease with which we made spectacular progress, and we cure almost 90% of patients when we have the drugs available,” Link said. “That particular crisis was averted with stopgap measures that we had in place, but we are not out of the woods yet by any measure.”

ASCO representatives have joined efforts to identify long-term solutions to the drug shortage crisis, calling on Congress to address the issue.

In May, both the House and Senate passed bills that would:

Require drugmakers to notify the government about potential drug shortages, including when they plan to discontinue or interrupt production. The federal government would have the ability to alleviate shortages by finding new suppliers, either within the country or overseas.
Introduce fees for the review of generic drugs and less expensive versions of biotechnology products. The generic drug fees are expected to reduce review times to one-third of current levels and improve the availability of generic products.

Leaders in both chambers are trying to reconcile the differences between the two measures, and they hope to forward compromise legislation to the president by early July.

The FDA has taken several steps to prevent drug shortages, such as managing a tracking database, sharing information with the Justice Department about companies that stockpile drugs and resell them at exorbitant prices, communicating with industry on production or quality control issues, and using regulatory discretion to help companies import products from overseas.

The agency also worked with Pfizer to resolve a shortage of doxorubicin, which is used to treat ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma.

“Pfizer went back into its portfolio to relaunch other sterile injection oncology drugs to bring alternatives to the market,” said Rear Adm. Sandra Kweder, MD, deputy director of the FDA’s Office of New Drugs.

The FDA lacks the authority to force manufacturers to increase production of drugs that are in short supply. However, since President Obama signed an executive order Oct. 31 to help prevent drug shortages, the FDA made significant progress, Kweder said.

Under current law, manufacturers are not required to report production difficulties to the FDA, but many have done so voluntarily. That is a key component of the effort to avert shortages, Kweder said.

“In 2012, 50 drug shortages have been prevented from early notification,” she said.

Most of the drugs in short supply have been inexpensive generics, said Richard L. Schilsky, MD, the hematology/oncology section chief at the University of Chicago and chairman of ASCO’s government relations committee.

Richard L. Schilsky

Although the business model is far from perfect and quality control issues are always a concern, generic drug manufacturers are not being driven out of business, Schilsky said.

“This is a multifactorial problem,” he said. “There are manufacturing, supply and distribution problems. There has been a lot of consolidation in the generic drug industry. There are relatively few companies actually making an investment to make generic drugs.”

Economic influences occur, but the cause of the shortage is manufacturing, according to Kweder. If one company makes 30 products and that company has a manufacturing problem, those 30 products suddenly are at risk of falling into shortage.

“Manufacturing and drug quality problems have accounted for — and continue to account for — the majority of drug shortages,” she said.

Disclosure:

Drs. Kweder, Link and Schilsky report no relevant financial disclosures.