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Extended version: Widespread drug shortages spur FDA policy revisions

Agency responds to executive order with new rules for drug makers

The magnitude and frequency of drug shortages facing patients, health care providers and the pharmaceutical industry have made the problem too clear to ignore. A problem that wasn’t on the general public’s radar screens just a few years ago today is overtaking mainstream headlines and consuming the drug and health care industries as they struggle to address the problem.

According to an October 2011 Food and Drug Administration (FDA) report, drug shortages nearly tripled between 2005 and 2010, from 61 shortages annually to 178. Most of those shortages—80 percent—involved injection drugs including oncology drugs, antibiotics, and electrolyte and nutrition drugs. Take injectable cancer treatments: While their use has increased by around 20 percent, production capacity hasn’t grown correspondingly.

The effects can be understandably devastating to patients who rely on these drugs to treat serious conditions. One lawyer declined to comment on this story because of the heartbreaking and personal nature of drug shortages—she is approached on a regular basis, she said, by patients and their family members demanding to know how this possibly could be allowed to happen today in the United States.

Drug shortages also can lead to hoarding and price-gouging. A report from the House Committee on Oversight and Government Reforms pointed to a leukemia drug typically priced at $12 per vial being sold for $990 per vial; this past August, the health care provider alliance Premier Inc. reported on a $25.90 blood pressure drug that, in the face of a shortage, was being sold for $1,200. Most drug shortages result from problems at the manufacturing facility, manufacturing or shipping delays and shortages of active pharmaceutical ingredients. Quality problems are particularly serious—some shortages have been caused by products found to be contaminated with glass shards or fungus.

“This is a problem we can’t wait to fix,” President Obama said in an Oct. 31, 2011, statement as he signed an executive order directing the FDA to take further action to prevent and reduce drug shortages.

The FDA has responded by issuing new rules and working more closely with drug manufacturers and other parties.

Notification Nudge

On the same day the president issued the executive order, the FDA sent out a letter to manufacturers of all marketed drugs, reminding them of their obligations to report potential shortages, but also encouraging them to provide voluntary notification beyond current requirements. In 2010, the FDA prevented 38 drug shortages; as of October 2011 it had prevented 99, an increase it attributes in part to improved notification by manufacturers. That’s only improving, says Valerie Jensen, associate director of the FDA Center for Drug Evaluation and Research’s Drug Shortage Program. As of December 2011, FDA staff is pleased with manufacturers’ response.

“We’ve had a sixfold increase in notifications [since sending out the letter],” Jensen says. “We used to get about 10 notifications a month, and in the four weeks after the executive order we got more than 60. Now we’re continuing to get that high rate.”         

The FDA has always encouraged companies to provide voluntary notifications—the sooner the agency knows about a potential problem, the sooner it can pitch in to help prevent or minimize the shortage by, for instance, asking other companies to increase production, working with manufacturers to address the dangers of quality issues and expediting review of regulatory submissions. 

Mandatory Reporting

While voluntary notification may be increasing, the FDA also has issued an interim final rule clarifying for manufacturers under what circumstances they must report discontinuations to the FDA under provisions of the Food, Drug and Cosmetic Act, which requires sole manufacturers of certain drugs to notify the FDA at least six months before they discontinue manufacturing a product. The rule clarifies how the FDA interprets “sole manufacturer” and also what a discontinuation means to the agency.               

“By ‘sole manufacturer’ we’re talking about the only company making even a specific strength of a drug, or a specific dosage form or presentation,” Jensen says. “And a discontinuation doesn’t just mean a permanent discontinuation—it also means if a firm is going to discontinue or shut down momentarily or temporarily. We want to know about anything that will temporarily or permanently impact supply.”

The rule broadens a previous FDA interpretation—in the past, only manufacturers that planned to permanently discontinue the manufacturing and marketing of a drug were subject to mandatory reporting. Jensen says the rule puts companies on notice that the FDA wants to know if they’re going to discontinue a drug, and it wants to know as soon as they do.

The interim final rule became effective Jan. 18, and the agency will take comments on it until Feb. 17. Jim Czaban, who chairs Wiley Rein’s Food & Drug Law practice, says the rule itself is a “drop in the bucket” in terms of the regulatory burden on drug companies. He also believes it’s unlikely to change much in the short term.

Systemic Problems

“As the FDA has recognized, the problem [results from] multiple factors that cut across a lot of different areas—there’s no magic bullet here,” Czaban says. “I don’t think the FDA is in a position to be able to solve the underlying fundamental problems, like whether it’s worth it for a drug company to be in the market for a particular drug … and the unbelievable pressure on drug pricing. Congress might be able to do something about that, but it would open a whole other can of worms.”

Another fundamental problem to which there are no easy answers is the key FDA priority of insisting on high-quality manufacturing operations.

“Some observers have pointed to this problem … [which] raises the question of how to reconcile these two objectives—i.e., avoid shortages and maintain high standards,” says Arnold Friede of Arnold Friede & Associates, former senior counsel at Pfizer. “I don’t know the answer, but the tension between the two is clear.”

What the FDA can do, Czaban says, is make improvements around the margins, whether it’s working more closely with companies facing manufacturing problems for a drug that could be in shortage, or expediting inspections and reviews for applications of drugs that may be in short supply.

In addition to encouraging voluntary notifications and issuing the interim final rule, the FDA is taking actions such as increasing staff dedicated to addressing drug shortages and implementing a database that can help analyze the characteristics of drug shortages. In the long term that could lead to the development of a data-driven model to help the FDA assess the probability of future shortages. Those are just a few of the many longer-term actions the agency plans to address a growing problem. 

“We are doing everything we can do, and we’ll continue to do so,” Jensen says.

Associate Editor

Melissa Maleske

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