U.S. Drug Shortage Could Threaten U.S. Health System

Sept. 23, 2011— -- A growing shortage of important chemotherapy drugs, anesthetics and antibiotics, which has compromised or delayed care for some U.S. patients and may have led to at least 15 deaths, represents a "pressing public health problem," a top federal health official said today.

At the same time, shortages of medications to treat cancer and infectious diseases have strained, disrupted or derailed hundreds of important research trials within the National Institutes of Health, said Dr. Howard K. Koh, assistant secretary of the Department of Health and Human Services. He called the disruptions "very troubling to us as a nation that prides itself on scientific advances."

Koh painted a picture for the House Energy and Commerce Subcommittee on Health in which even the Food and Drug Administration, the federal agency responsible for assuring the safety of the U.S. drug supply, has been caught unaware when particular drugs have become scarce -- or impossible to get. "Oftentimes, the FDA does not know until it is too late, and then patients are stuck in this dire situation, and that's just not acceptable," Koh told lawmakers.

"We still have a large percentage of actual shortages where we were not aware that it was coming," Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research, told the panel.

In the last 15 months, at least 15 patients have died either because the proper or preferred drug wasn't available, or because of complications with substitute medications, according to an Associated Press review of industry reports and interviews with nearly two dozen experts. In the worst of those cases, AP reported, nine Alabama patients on feeding tubes died and 10 others were harmed because the sterile premixed nutritional solution they would normally have received was unavailable and they instead received their nutrition from a hand-mixed batch that became contaminated by bacteria.

One possible solution to the problem would be to find a way for manufacturers "to report impending supply disruptions and discontinuation of drug," Koh said. "The sooner FDA learns of a drug shortage, the more effective it can be in helping to notify providers and minimizing the impact on patients."

The FDA doesn't have the power to require companies to report impending shortages. However, the proposed Preserving Access to Life-Saving Medications Act would give the agency the authority to require advance notification from drug manufacturers when life-saving drugs are in danger of becoming unavailable. The American Cancer Society Cancer Action Network, an affiliate of the American Cancer Society, today announced its support for the legislation.

As of Friday, 209 drugs were on the current shortage list compiled by the American Society of Health-System Pharmacists, based in Bethesda, Md., and some of them are the heaviest-hitters in cancer treatment and the battles against increasingly drug-resistant antibiotics.

So far this year, the FDA streamlined a process so that five critically needed drugs unavailable from U.S. manufacturers could be imported temporarily from overseas, said Shelly L. Burgess, an FDA spokeswoman. "We can't always find a firm willing and able to import, but when we do, we evaluate the overseas drug and the facility it's made in to make sure FDA quality standards are met and that the overseas drug is safe for U.S. patients." One young patient at the NYU Langone Clinical Cancer Center this week received intrathecal thiotepa (chemotherapy injected directly into the spinal fluid) imported from Europe with FDA permission, said Dr. James L. Speyer, medical director of the center.

Shortages Force Medical Centers to Use Substitutes

Speyer, who has spoken openly about the shortages at NYU, said today that the cancer center has re-established short-term supplies of some key drugs through "legitimate supply sources" and "purposefully" chose not to deal with so-called gray market suppliers, who buy up quantities of drugs and re-sell them at higher prices. At the Beebe Medical Center in Lewes, Del., Sam Roberts, director of pharmacy, said the medical center views the gray market as a last resort. In 2010, "we purchased a drug for $600 that we normally would pay $25 for. We did not pass any of that additional cost on to patients."

In an interview on Aug. 25, Speyer said NYU was "cold out" of a key drug used frequently for gastrointestinal malignancies, 5-fluorouracil (5-FU). During the week of Aug. 22, "we had over 30 patients who had their treatment delayed or changed to capecitabine (Xeloda)." Some patients had trouble tolerating the oral drug while others faced unaffordable co-pays for the more expensive substitute.

Speyer said a month of 5FU costs the medical center about $30; a month of capecitabine costs about $3,000. During the shortage, he was put in the heartbreaking position of telling Medicare recipients who couldn't afford a $250 co-pay that he couldn't treat them. "Sometimes you just look across the bed and say 'this is what I have,'" Speyer said. A month later, with enough 5FU on hand to get through the next one to two months, there's no way to know how those who went untreated for a month may have suffered, he said.

In late August, paclitaxel, an important treatment for ovarian, breast and lung cancers, was in such short supply, "we were not able to enter any patients into clinical trials that required (paclitaxel) because we couldn't guarantee the drug for the course of treatment." Since then, Speyer said, "we have started to re-enter patients in trials" on the drug.

NYU is still grappling with a shortage of the drug Doxil, and no patients beginning chemotherapy are getting it. However, a program by the drug's manufacturer, "got off to a bit of a rocky start for us," he said. Janssen Products initially was going to supply enough Doxil for just four of the 48 NYU cancer patients who already were taking and benefiting from Doxil. Since then, he said, "about two-thirds of our people are now getting the drug."

Doxil is unusual because it's one of the few oncology drugs still protected by a patent. Most of the shortages have affected older, generic injectable or intravenous drugs that have been on the market for decades, and are only marginally profitable. That has left fewer companies to make them.

One particularly disturbing consequence of the industry consolidation and the concomitant aging of manufacturing plants has been quality control, Koh said. "We literally are tracking products that have particulate matter, even pieces of glass and pieces of metal in what should be sterile products that are injected into patients."

Kweder said the FDA is willing to work with companies "to help them develop solutions to fix the problem and avoid interruption in production. That is not always possible," she said. "It's simply not always possible."

FDA Encourages Collaborations with Industry to Ensure Supply /h2>

Koh told lawmakers that "although the FDA cannot require firms to continue production of a product or increase production in response to a shortage, it does encourage other firms to do so." Collaborations with drug companies averted 38 shortages last year. So far this year, he said, "I am pleased to report that for the first time, 99 shortages have been prevented."

The drug shortages also are boosting expenses for medical centers. At Henry Ford Hospital in Detroit, Megan Winegardner, coordinator of medication policy and safety for the pharmacy services department, said that as of Friday, "there are 26 medications in short supply today for which we have implemented some sort of alternative plan (restricting use, recommending alternatives, etc.)." Winegardner estimated that her department has doubled, from 20 to 40, the number of hours it devotes weekly to managing drug shortages.

At the University of Washington Medical Center in Seattle, shortages "are still having a profound effect on patient care," which includes being unable to provide some kinds of therapy, said spokesman Dean Forbes. The medical center hired a new pharmacist whose responsibilities include tracking drug shortages throughout the university and the Seattle Cancer Care Alliance, he said.

On Monday, the FDA will hold a daylong public meeting to discuss drug shortages, Koh said. At the session, Dr. Arnold J. Berry will discuss an April survey conducted by the American Society of Anesthesiologists, which found 98 percent of more than 1,350 U.S. anesthesiologists (and 23 others from Canada, Switzerland, Qatar and Brazil) experienced a shortage of at least one anesthetic in the last year. Nearly half the respondents reported patients having "a less optimal outcome" because of the scarcity of important anesthesia drugs.

Koh told lawmakers that "although the FDA cannot require firms to continue production of a product or increase production in response to a shortage, it does encourage other firms to do so." Collaborations with drug companies averted 38 shortages last year. So far this year, he said, "I am pleased to report that for the first time, 99 shortages have been prevented."

The drug shortages also are boosting expenses for medical centers. At Henry Ford Hospital in Detroit, Megan Winegardner, coordinator of medication policy and safety for the pharmacy services department, said that as of Friday, "there are 26 medications in short supply today for which we have implemented some sort of alternative plan (restricting use, recommending alternatives, etc.)." Winegardner estimated that her department has doubled, from 20 to 40, the number of hours it devotes weekly to managing drug shortages.

At the University of Washington Medical Center in Seattle, shortages "are still having a profound effect on patient care," which includes being unable to provide some kinds of therapy, said spokesman Dean Forbes. The medical center hired a new pharmacist whose responsibilities include tracking drug shortages throughout the university and the Seattle Cancer Care Alliance, he said.

On Monday, the FDA will hold a daylong public meeting to discuss drug shortages, Koh said. At the session, Dr. Arnold J. Berry will discuss an April survey conducted by the American Society of Anesthesiologists, which found 98 percent of more than 1,350 U.S. anesthesiologists (and 23 others from Canada, Switzerland, Qatar and Brazil) experienced a shortage of at least one anesthetic in the last year. Nearly half the respondents reported patients having "a less optimal outcome" because of the scarcity of important anesthesia drugs.