Roxanne Nelson

June 07, 2012

June 7, 2012 (Chicago, Illinois) — The good news is that early notification requirements established by the US Food and Drug Administration (FDA) have prevented 50 drug shortages this year. The bad news is that drug shortages persist, with oncology products being particularly hard hit.

Even though the FDA, drug manufacturers, and other stakeholders have taken steps to address the underlying causes of the problem, drug shortages are expected to persist for the foreseeable future, said Richard Schilsky, MD, professor of medicine at the University of Chicago, Illinois, at a session here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

"The crisis has been particularly bad in cancer care," Dr. Schilsky said. "Because many of the mainstays of treatment are drugs that are decades old — generic, injectable, and irreplaceable — in many cases, there are no acceptable medical substitutes."

In many cases, patient care has been threatened as a result of drug shortages, explained Dr. Schilsky, who is past president of ASCO and current chair of the ASCO Government Relations Committee.

"Over the past 2 years, 22 therapies have been in short supply in oncology," said Michael P. Link, MD, ASCO president and professor of pediatrics at Stanford University School of Medicine in California. "While in some cases there are work-arounds and substitutes that exist, for other drugs, there really are no replacements available. Without them, we're faced with the option of delivering suboptimal therapy, more costly care; if there is a work-around available, it may be at a higher cost."

Ongoing and Chronic Problem

The shortage of critical drugs has been an ongoing issue. According to the FDA, the number of drugs deemed to be in short supply nearly tripled from 2005 to 2010 (from 61 to 178). In 2011, roughly 200 shortages were reported. Many of the products in short supply are generics, primarily sterile injectables, and include cancer medications, anesthetics, and antibiotics.

Dr. Link noted that some of the most "essential mainstays" of treatment for both children and adults — especially curative therapies — are currently in short supply. These include cisplatin, mustragen, fluorouracil, and paclitaxel. "In some cases, we have temporarily addressed the threat to patient care as 1 or 2 manufacturers have stepped up production, but other companies are still reporting problems," he said. "Long-term availability of these vital medicines remains uncertain."

As previously reported by Medscape Medical News, steps were recently taken to avert critical shortages of doxorubicin (Doxil) and a version of methotrexate.

The FDA approved a new manufacturer of a preservative-free form of methotrexate, and another supplier ramped up its production of this version of methotrexate. For doxorubicin, the FDA allowed the temporary importation of Lipo-Dox from the Indian manufacturer Sun Pharma Global.

The shortage of methotrexate was averted at the last minute, Dr. Link explained, but another problem is looming. High-dose infusions of preservative-free methotrexate are given as a curative treatment for many childhood cancers, but now there is a shortage of sodium bicarbonate. "That is basically baking soda in a bottle, but it's necessary to administer the methotrexate," he said.

Community Practices Hardest Hit

Drug shortages are often felt most acutely in community practices, where the majority of adult patients receive their cancer care. "These practices don't have the pharmacy staff or other resources found in larger hospitals to secure adequate supplies of drugs that are in short supply," said Dr. Link.

Panelist Charles Penley, MD, incoming chair of the ASCO Government Relations Committee, is a community oncologist and part of a very large practice in Nashville, Tennessee. He pointed out that they are in a better position than many groups, since they are large enough to be able to generally locate products. "We have experienced drug shortages intermittently over the past few years, but the shortages didn't become acute until the early spring of 2011," Dr. Penley explained.

"We are in a better situation than other practices, but we have had trouble getting the drugs to provide daily care for our patients," he said. He pointed out that his group has an employee whose sole job is "to make sure we have drugs on hand for every clinic every day."

"This adds an administrative burden to our practice, but we need someone on the ground to make sure we have the drugs we need," Dr. Penley explained.

Injectables Most Prone to Shortages

The generic versions of sterile injectable cancer medications are most prone to shortages, which are often caused by manufacturing and quality problems. For example, a manufacturer recently discontinued production when metal shavings or particles of glass were detected in a product, noted Sandra Kweder, MD, deputy director of the Office of New Drugs at the FDA. The closing of a single facility, even temporarily, can lead to shortages, she noted.

"Prevention of drug shortages at the FDA is a priority; it is also a priority of Congress and the president," Dr. Kweder said.

"We have made progress." She explained that 150 drug shortages have been prevented since October 2011; in 2012, another 50 have been prevented, simply because of early notification from manufacturers. But she noted that although oncology drug shortages are a pressing concern and that the FDA has been working with drug manufacturers, they cannot compel a company to produce a certain drug.

Not Enough Teeth

ASCO is seeking a permanent solution to the problem of drug shortages, and Dr. Schilsky believes that this will require an Act of Congress. New legislation has recently been approved in the Senate and House that includes measures designed to ward off shortages. But ASCO is calling on Congress to require manufacturers to give the FDA early warning of impending shortages and to have some sort of penalties or fines for companies that do not comply.

The reporting requirement is in the legislation, but the penalties are not, Dr. Schilsky noted. "If there are no teeth in that legislation, some companies may decide not to report as required," he said.

Dr. Schilsky explained that a provision to impose cash penalties on companies that do not comply has not been met with enthusiasm and is not likely to be included in the final bill.

ASCO also believes that Congress should think about providing appropriate economic incentives for companies to develop drug-shortage contingency plans. We would also like Congress to "mandate that the provisions addressing generic drug shortages also apply to biologics," Dr. Schilsky said. "At the moment, most of the biologics used in cancer treatment are branded, but they are eventually going to become generics."

The current legislation would require generic drug makers to pay user fees to federal regulators for the first time. The addition of these fees could bring about $1.5 billion to the FDA in additional resources over the next several years, explained Dr. Schilsky.

"That should reduce the review time for a New Drug Application to market a generic drug from the current 30 months down to 10 months or less, which would be a huge step forward in terms of getting new manufacturers into the game and getting drugs to market," said Dr. Schilsky.

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