By Tom Wilemon and Walter F. Roche Jr. | The Tennessean
Nearly 150 patients who were exposed to potentially contaminated
steroid injections in Tennessee got medicine that was more than 7 weeks
old, even though industry guidelines say its shelf life should have been
no longer than 24 hours.
Almost one in five of those patients
developed fungal infection -- a rate dramatically higher than for those
who were 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, including 13 in Tennessee.
guidelines from the U.S. Pharmacopeia Convention, the drug would be
considered a "high-risk" product -- made from nonsterile ingredients and
lacking antimicrobial preservatives. 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.
Tennessee, NECC'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.
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 mass-produced to begin with, said Loyd V. Allen Jr.,
editor-in-chief of the International Journal of Pharmaceutical
"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."
NECC 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
percent infection rate, while those treated with newer vials had only a 3
percent 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
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 released by the state health department,
was Saint Thomas Outpatient Neurosurgery Center.
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.
Michael A. Carome, deputy director of health research for Public
Citizen, a nonprofit that advocates for public safety, said the medical
journal article is further proof that New England Compounding violated
"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."