Caroline Helwick

October 17, 2012

Despite "summits," public workshops, and executive orders from the White House, drug shortages remain critical and clinicians continue to scramble to procure necessary drugs or acceptable substitutes.

At a session held during Anesthesiology 2012: American Society of Anesthesiologists (ASA) 2012 Annual Meeting, speakers addressed the current status of the drug shortage while anesthesiologists seized the opportunity to air their frustrations.

"I feel like a drug dealer for what I am forced to do to obtain the drugs I need," one attendee shared.

Barbara Leighton, MD, chief of obstetric anesthesiology at Washington University in St. Louis, Missouri, told Medscape Medical News she was currently trying to find preservative-free morphine for intrathecal and epidural use. She has just learned that her current supplier, Ameridose — already a back-up choice — shares the same owners as New England Compounding, the source of the ongoing fungal meningitis outbreak, and was also being investigated for possible safety issues.

"We quit using Ameridose morphine immediately," she said. "I have spent enormous time over the last 2 days looking for other legitimate suppliers instead of enjoying the meeting."

Drug Shortages Not Easing

In 2011, there were 267 drugs in short supply, and 75% of these involved sterile injectables. On the basis of current figures in 2012, "we are on track to bypass the 2011 shortage," said Peter Schoenwald, MD, from the Cleveland Clinic in Ohio.

Captain Valerie Jensen, RPh, associate director of the Center for Drug Evaluation and Research (CDER) Drug Shortage Program at the Food and Drug Administration (FDA), maintained that the government is doing all it can to assuage the problem and pave the way for a more secure future.

"Our mission is to prevent, mitigate, and help resolve shortages," she said, noting that the CDER employs 11 full-time staff to attend to the crisis. "Most shortages do get resolved," she said. "We prevented 195 shortages in 2011, mostly due to firms notifying the FDA of early problems."

But she acknowledged that "FDA authorities are very limited." The agency can require notification by manufacturers of supply disruptions, delays, and discontinuations (under the new FDA Safety and Innovation Act [FDASIA] requirement). In the case of controlled substances, the FDA can request that the attorney general increase quotas so that other manufacturers can address the gap.

But, she added, there is no penalty for not reporting. The FDA cannot mandate a company to make a drug or even make more of a drug, nor can it dictate how much and to whom a drug is sold or distributed.

Sterile Injectables: Reasons for Shortages

Quality issues account for about 50% of the shortages of sterile injectables. Often, this pertains to the detection of particulate (foreign matter such as glass, metal, fibers) in the product, bacterial and mold contamination, and equipment breakdown. As facilities age, these problems are growing, Jensen said.

The good news — but still 5 years away — is that many companies are "retrofitting" to upgrade their production facilities and others are building new facilities altogether.

ASA 2012 Survey

Arnold J. Berry, MD, MPH, from Emory University in Atlanta, Georgia, who is ASA vice president for scientific affairs, reported the results of a survey assessing the impact on anesthesiologists. This is a follow-up to the first survey conducted in April 2011.

In March 2012, of the 3063 responders, 98% were currently experiencing a drug shortage, especially for fentanyl (66%), succinylcholine (21%), propofol (15%), and pancuronium (15%). In 2011, the most frequent shortages were propofol (88%), succinylcholine (80%), neostigmine (52%), and epinephrine (17%).

More than two thirds reported that their patients experienced a suboptimal outcome, such as postoperative nausea and vomiting, and more than half said procedures and recovery time were longer. Six deaths (0.2%) were suspected of being related to a drug shortage. In addition, 96% of respondents had to use alternative drugs, 50% had to alter procedures, and 11% had to postpone or even cancel cases.

The survey indicates "clear concerns for patient safety," Dr. Berry said. He cited the potential for infection risk from splitting 50-mL or 100-mL vials of propofol among more than one patient, along with medication errors, such as incorrect doses due to unfamiliarity with substituted drugs.

The alternative pathway, the "gray market," also creates cause for concern, he added. Although complaints have centered on the high cost of drugs obtained through these channels, anesthesiologists should be concerned about the quality of these products as well, he said.

"These drugs pass through multiple middlemen. Not only does each mark up the price, but their facilities may not be equipped for proper storage that would help ensure quality. You have to understand the pedigree, the history, of the product."

Complaints about the gray market are being forwarded by the FDA to the Department of Justice for investigation.

Beyond the Gray Market

But Joel Zivot, MD, from Emory University, said the gray market is "not the real problem" but a "red herring." Dr. Zivot helped lead the ASA/Emory-sponsored Consensus Conference on the Ethics of Drug Shortages in June 2012.

Noting that gray markets are not illegal, he suggested that the term given for this alternative supply route "suggests it's something nefarious, but it's not." Instead, Dr. Zivot maintained the root of the problem lies within the complex purchasing contracts between manufacturers and groups that join together to create pricing leverage.

"There are not enough manufacturers, but there are also not enough buyers. Fewer people in the marketplace affect the supply chain," he said. "It's not a free market or a regulated market. It's the worst of both worlds."

Anesthesiologists Say Their Hands Are Tied

John Sconzo, MD, an anesthesiologist practicing at Glens Falls Hospital, New York, drew applause when he questioned the need to use a single vial for a single patient. "What is the data showing it is unsafe to take a 5-mg vial of midazolam and break it down for different patients? I'm talking about one physician using different syringes, not handing if off. We have been doing this for years, and it's gotten vilified. We are facing these shortages, we can't use our clinical judgment, and we are wasting drug."

Dr. Berry responded, "There are rules in place on appropriate sterile techniques to prevent catastrophic outcomes. If all goes okay you may be able to do this, but you can look in the literature and find outbreaks where prescribed infection control practices led to significant infection of patients," he said. "We have to advocate for best practice. The downside is this leads to drug wastage in a time of shortage. That's the tension we are facing."

Dr. Zivot had the final word. "We don't want to be in a situation to have to do that. Our interest is taking care of patients," he said. "The problem is that other people in this story have different interests. Being responsible stewards of a little supply and dividing that into smaller and smaller portions is not the real issue. This is a man-made problem, and it can be fixed by man, but so far it's not."

Dr. Schoenwald, Dr. Berry, Dr. Zivot, Dr. Sconzo, and Dr. Leighton and Ms. Jensen have disclosed no relevant financial relationships.

Anesthesiology 2012: American Society of Anesthesiologists (ASA) 2012 Annual Meeting. Presented October 16, 2012.