Persistent sterile injectable drugs shortages put patients at risk

Hospitals experiencing a shortage of generic sterile injectable drugs will likely see a spike in their mortality rates, according to a new study.

Researchers have found a "strong and consistent" link between between norepinephrine shortages and increased septic shock mortality rates in hospitals, according to a study published Tuesday in the Journal of the American Medical Association. Norepinephrine is the primary treatment for septic shock, which is one of the leading causes of death in hospitals. Without it, hospitals have to pay more for substitute drugs.

Mortality rate for septic shock patients increased 3.7% during norepinephrine shortages, from from 35.9% during non-shortage quarters to 39.6% during shortage quarters, according to 2008-2013 data from 26 hospitals analyzed in the JAMA study.

"It shows that shortages are more than just inconveniences and labor intensive for pharmacies – there is real patient harm when shortages occur," said Erin Fox, director of drug information at the University of Utah Health Care's drug information service.

Norepinephrine is one of many sterile injectable drugs that are especially prone to shortages due to high storage costs that translate to low profit margins. These drugs require specialized production and can be susceptible to quality problems during the manufacturing process, and subsequent scarcities can create medical crises for both hospitals and patients.

Currently, two of the three U.S. manufacturers have adequate norepinephrine supply while Pfizer lists a shortage due to manufacturing delays but estimates the issue will resolve this month, according to the American Society of Health-System Pharmacists.

Including high-priority drugs in the Strategic National Stockpile that assembles large quantities of drugs to be used in emergency, disseminating quality data on manufacturers and changing policy to incentivize increased production may prevent future crises, the study recommended.

While the Cleveland Clinic has never run out of norepinephrine, it has had to hire a full-time drug shortage pharmacist because shortages are such a common problem, said Dr. Scott Knoer of Cleveland Clinic.

PharMEDium, a division of major drug distributor Amerisource Bergen, has experienced norepinephrine vial shortages in part due to the limited number of FDA-approved manufacturers, the company said.

Generic drug manufacturers typically limit production to an often outdated single facility given the significant expense, which can essentially halt production in the event of equipment failure or quality control problem.

An early warning system implemented in 2012 helped prevent hundreds of shortages, according to the FDA. It requires that drug manufacturers promptly notify the agency of manufacturing disruptions as well as provide mitigation strategies.

The study recommends that the FDA adopts a grading scheme when it inspects manufacturing facilities to change the focus from closing plants to improving quality and making those results readily available to purchasers. Expanding the Strategic National Stockpile to include other high-priority drugs based on their risk of shortage and clinical consequence as well as requiring manufacturers to include projections of demand and plans to meet that demand could prevent shortages, the study said.