FDA adds 2 makers of cancer drugs

TRENTON, N.J. -- Federal regulators have approved new suppliers for two crucial cancer drugs, easing critical shortages that had been ratcheting up fears that patients, particularly children with leukemia, would miss lifesaving treatments.

But there are currently 283 separate prescription drugs in short supply or unavailable nationwide, and regulators and manufacturers say shortages are a long-term problem that will continue to give patients and doctors nightmares.

On Tuesday, the Food and Drug Administration said it will temporarily allow importation of a replacement drug for Doxil, a drug for recurrent ovarian or bone marrow cancer. The Johnson & Johnson drug hasn't been available for new patients for months because J&J's contract manufacturer had to shut down production over serious quality lapses.

The FDA also has approved a new supplier for a preservative-free version of methotrexate, a crucial drug for children with a type of leukemia called ALL, for lymphomas and for the bone cancer osteosarcoma. The version with preservatives, the one that's been scarce, can be toxic or cause paralysis in children and other patients getting the drug either by injections into spinal cord fluid or at very high doses.

The FDA also has approved the release of a batch manufactured by Ben Venue Laboratories Inc., shortly before it closed several factories at its complex in Bedford, Ohio, due to serious quality problems. That closing was what turned the periodic methotrexate shortage that began in late 2008 into a crisis almost overnight, with fears that kids would begin missing treatments within weeks.

"We have made real progress ... We believe that (suppliers) will be able to meet the demands of patients in the U.S. market" for the two drugs indefinitely, FDA Dr. Commissioner Margaret Hamburg told The Associated Press in an exclusive interview. "It's a huge relief for us."

Numerous medical and drugmaker groups, along with the White House, applauded the news but cautioned that much still must be done to resolve all the problems causing shortages.

The FDA increasingly has been able to prevent shortages, mainly due to a sixfold increase in manufacturers voluntarily notifying the FDA when they anticipate shortages and agency efforts to expedite any approvals needed for new production lines, Hamburg said.

Thanks to such notice, the agency prevented 195 drug shortages in 2011, mostly late in the year after President Obama issued an executive order giving FDA additional resources to address the shortages. Hamburg said companies have been "very responsive" when FDA asks them to boost production after another company warns it will halt a drug's production.

In the latest case, the FDA has temporarily allowed importation of an alternative to Doxil called Lipodox, made by Sun Pharma Global FZE. The Indian drugmaker already sells products in the U.S., and its factory has been inspected.

The FDA is allowing APP Pharmaceuticals LLC to make the preservative-free version of methotrexate in addition to its current drug with preservatives. The company had made a preservative-free version years ago, but needed to update paperwork and meet other requirements, which the FDA expedited.

"Within the next four to six weeks, we can supply clinics with this drug," Mitchell L. Ehrlich, a vice president with APP parent Fresenius Kabi USA, said during a Washington news conference announcing the new steps.

Ehrlich said his company previously helped resolve serious shortages of other important drugs, such as by increasing production of doxorubicin -- which treats several types of cancer -- from 10 percent of the market supply to 60 percent.

Hospira Inc. on Monday began shipping 31,000 vials of preservative-free methotrexate, more than enough to meet a month's U.S. demand, to hundreds of hospitals and treatment centers, said its CEO, Mike Ball. He said the company will ship another 34,000 units next week and 55,000 more in mid-March to build a supply cushion. It's also now transporting from around the world to its Australian factory about 100 kilograms of methotrexate's active ingredient -- enough to make about a three- to four-month supply.

Two other companies, Mylan Inc. and Sandoz Inc., also are ramping up their production of preservative-free methotrexate.

Still, hundreds of other drugs remain in short supply, including at least six for cancer.

"I don't think we can ever close the book on drug shortages," Hamburg told The AP. "I think we will always have to be vigilant."

Drug shortages have increased dramatically in the U.S. over the past six years, particularly for generic injected drugs. They are the workhorses of hospitals but are difficult to make and produce little profit for drugmakers. At least 15 deaths since 2010 have been blamed on the shortages.

Doctors have had to resort to second-choice drugs that don't work nearly as well, have more-serious side effects or cost much more than one unavailable. For some drugs, there simply isn't a good alternative.

So far this year, 27 new shortages have been reported, and about 215 that began in 2010 or 2011 remain unresolved, according to Erin R. Fox, manager of the University of Utah Drug Information Service, which tracks shortages.

"At this time last year, we were on a pace of about one new shortage per day. Thanks to FDA's hard work, that pace is cut in half for this first part of 2012," Fox said.

The shortages are caused primarily by problems with sterility and other serious issues that have led to shutdowns of production lines and occasionally entire factories.

In addition, consolidation among generic drug manufacturers, as well as manufacturers deciding to end production of marginally profitable drugs, has led to decreased capacity. That means when one manufacturer suddenly stops production, the small number of others making a drug can't quickly pick up slack. And for some drugs, demand has increased.

The inability to get crucial medicines has disrupted not only carefully timed chemotherapy regimens, but surgery and care for patients with infections, pain and other serious conditions.

Meanwhile, some unscrupulous smaller distributors, dubbed "gray marketers," have been exacerbating shortages by charging hospitals many times the normal price for drugs that can't be acquired through normal suppliers. Several bills in Congress are pending that would establish penalties for drugmakers that don't give notice of impending shortages, or by setting penalties for price gouging on prescription drugs.

Of late, the cancer drug shortages have attracted the most attention, partly because missing multiple treatments can sharply reduce the chances of curing the disease.

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Linda A. Johnson can be followed at http://twitter.com/LindaJ--onPharma

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FDA adds 2 makers of cancer drugs