The Exserohilum rostratum fungus is the primary cause of a number of meningitis illnesses afflicting people who got steroid injections for pain.(Photo: CDC via AP)
NASHVILLE -- Nearly 150 patients exposed to potentially contaminated steroid injections in Tennessee received medicine more than 7 weeks old, even though industry guidelines say its shelf life should have been no longer than 24 hours.
Almost 1 in 5 of those patients developed a fungal infection - a rate dramatically higher than for those treated with fresher medicine, according to the Tennessee Department of Health.
The methylprenisolone acetate produced by Massachusetts-based New England Compounding Center is blamed in a nationwide outbreak of fungal meningitis that has sickened 424 people and killed 31 in 19 states.
Under best-practice guidelines from the U.S. Pharmacopeia Convention, the drug would be considered a "high-risk" product - made from nonsterile ingredients and lacking antimicrobial preservatives, according to what the compounding center director told the FDA. In the absence of a sterility test, storage time should not exceed one day at room temperature or three days at a cold temperature, the guidelines say.
In Tennessee, the compounding center's vials were stored at room temperature, as specified in the package instructions, state health officials said in a paper published Tuesday in the New England Journal of Medicine. And those who received the medicine expected it to be sterile, said one author of the study, Dr. Tim Jones, Tennessee's state epidemiologist. If it had been, no fungus would have grown in the vials.
The compounding laboratory claimed to have performed sterility tests on its products, but the Massachusetts Board of Pharmacy has said that testing was inadequate and shipments were made before the safety of medicines had been verified.
The preservative-free steroid should never have been produced en masse to begin with, said Loyd V. Allen Jr., editor-in-chief of the International Journal of Pharmaceutical Compounding.
"If it is not preserved - if it is only intended to be used in one patient - then it has to be packaged in a single-use container and its contents have to be used all at one time," Allen said. "If it is going to be used on multiple patients or at multiple times, then it has to have a preservative."
New England Compounding Center violated its license by mass-producing drugs without prescriptions for individual patients, according to officials with the U.S. Food and Drug Administration and the Massachusetts Board of Pharmacy.
The company shipped 17,676 units of preservative-free methylprednisolone acetate that have been linked to the outbreak. A sterility test should be conducted for any batch larger than 25 units, Allen said.
The state health department's analysis of infection cases in Tennessee found that patients treated with medicine packaged longer than 50 days had a 19% infection rate while those treated with newer vials had only a 3% infection rate.
"We found a strong association between the age of methylprednisolone vials and the rate of infection in one clinic," the physicians wrote. "One possible explanation for this observation is that the level of contamination in the vials may have increased over time with subsequent higher fungal burdens present in older vials."
The article does not identify the clinic by name but does note that the clinic had used 1,663 vials of the medicine. The only one of the three clinics in Tennessee that had that much product, according to prior information from the state health department, was St. Thomas Outpatient Neurosurgery Center.
However, Allen said the responsibility for providing guidance on shelf life rests with the drug manufacturer or compounding lab. The best-practice standards do allow compounding labs to recommend usage for up to six months if certain criteria, including a program for sterility testing, are met.
Dr. Michael A. Carome, deputy director of health research for Public Citizen, said the medical journal article is further proof that New England Compounding violated its license. Public Citizen is a non-profit that advocates for public safety.
"Had each dose of the drug been prepared on demand and as needed for individual patients consistent with the traditionally narrow scope of a compounding pharmacy, then each dose - even if contaminated - likely would have been used very soon after production, thus minimizing the risk to the patient because there would have been less time for the fungus to grow and multiply."
Tom Wilemon and Walter F. Roche Jr., The (Nashville) Tennessean