Risky drug-compounding method rarely used, survey finds

(Story updated with FDA information at 5:10 p.m. ET.)

The method for mixing drugs that led to 53 deaths in an outbreak of fungal meningitis in 20 states last fall is inherently risky, but seldom-used by hospitals, a new survey finds.

Meanwhile, officials with the Food and Drug Administration are wrapping up final inspection reports on 31 drug-mixing facilities that were examined for safety issues in the past seven weeks. Copies of the reports are publicly posted on the FDA's website. All but one of the companies received a report documenting “objectionable conditions.”

“During the course of both our proactive and reactive inspections over the past few months, we observed concerning sterility practices, inappropriate conditions for sterile processing and other practices that create risk of contamination,” FDA Commissioner Dr. Margaret Hamburg wrote on her blog Thursday.

The new survey of U.S. hospitals by HHS' inspector generals' office finds that the risky drug-mixing technique—known as “nonsterile-to-sterile” drug compounding—was used for only 666 doses per year in larger hospitals, or less than 1% of the time. The less-risky “sterile-to-sterile” drug mixing method was used more than 200,000 times per year in larger hospitals. Only 25% of the hospitals used any nonsterile-to-sterile mixed drugs at all.

Drug compounding is a method that pharmacists have long used to tailor bulk drugs for individual use, for example to convert pill-based medications in injectable form. However, recent drug shortages have caused hospitals to rely on mass-produced compounded drugs as a way to preserve the shelf life of sought-after medications and stretch limited supplies.

More than 99% of all drug compounding involves mixing sterile drug products in sterile solutions, the HHS inspector general's survey of 236 hospitals found.

The most risky method of drug-mixing, which was implicated in the meningitis outbreak that began at the New England Compounding Center last fall, involves the combination of nonsterile products that have to be mixed and then sterilized in facilities that are closely monitored for cleanliness. Opioids, steroids, electrolytes and diuretics are commonly involved in nonsterile-to-sterile mixing.

The survey said that about 85% of all hospitals that used nonsterile-to-sterile drugs bought them from outside pharmacies like the NECC rather than mixing them in-house.

“Few hospitals (11 of 236 hospitals) in our sample reported problems with product contamination,” the inspector general's report says. “However, as shown by the meningitis outbreak in fall 2012, any instance of product contamination has the potential for serious consequences.”

The Centers for Disease Control and Prevention says that flaws in compounding steroid injections at the New England Compounding Center have led to 733 known cases at last count, including 259 in Michigan and 152 in Tennessee.

Since the outbreak, more than half of the hospitals in the survey have asked their compounding pharmacies to provide more information on quality control, and more than 40% have changed which pharmacies they use.

Hamburg's blog post said the FDA's inspections over the past seven weeks have already led to changes among compounders, including voluntary product recalls and temporary stops in production to correct deficiencies.

“These inspectional observations reveal that there continues to be reason for concern about sterility deficiencies and other problems in some compounding pharmacies across the country—problems that could potentially affect the health of patients,” Hamburg wrote.

Follow Joe Carlson on Twitter: @MHJCarlson