As scientists and researchers across the country race to figure out why hundreds of patients have contracted fungal meningitis from pharmaceuticals compounded by the New England Compounding Center (NECC) and how to prevent future outbreaks, preliminary results from the Tennessee Fungal Meningitis Investigation Team were published this week in the New England Journal of Medicine.
One notable finding was a “strong association between the age of methylprednisolone vials and the rate of infection in one clinic.” At this clinic, 19% (29/149) of patients who were exposed to vials more than 50 days old contracted a fungal infection, compared with only 3% (6/190) of patients who received newer vials.
“One possible explanation for this observation is that the level of contamination in the vials may have increased over time,” the researchers wrote, noting that injectable, preservative-free glucocorticoid preparations have been previously shown to support fungal growths. Other factors that significantly increased the possibility of contracting meningitis were age older than 60 years and female sex.
The researchers also noted the prevalence of strokes as a “striking feature of this outbreak.” Of the 66 cases the team analyzed, 13 involved a stroke. The strokes were more common early in the outbreak, the researchers observed, “with four patients presenting with stroke less than 48 hours after the onset of any symptoms. The incidence of stroke declined as diagnostic testing became more prevalent and aggressive and patients were identified earlier in their clinical course.” No patients who were treated within the first 48 hours experienced a stroke, the researchers found.
In another article published in New England Journal of Medicine this week, Kevin Outterson, JD, analyzed the current regulatory outlook for compounding pharmacy, reviewing FDA’s efforts “to regulate industrial-scale compounding” over the last 20 years.
Outterson noted that NECC appears to have violated at least four of FDA’s compounding guidelines, including compounding without valid prescriptions, using commercial-scale manufacturing or testing equipment, producing a preservative-free version of a commercially available drug, and failing to conform with Massachusetts state law. He added, however, that “without information about the actual conditions in compounding pharmacies, regulators cannot act to address violations.”
Outterson also pointed out that “contamination is only one of five categories of risk associated with compounding pharmacies; the others are subpotency, superpotency, overmedication, and medication replacement.” To reduce all these potential risks, he suggested “enhanced transparency for state-level regulation, mandatory disclosures to physicians and patients, mandatory reporting of adverse events, user fees to support oversight, clear FDA authority to register and inspect nontraditional compounding pharmacies, enhanced incentives for internal whistleblowers, and modification of reimbursement rules to blunt the economic incentives driving industrial-scale compounding.”
Last, Outterson noted that “patients received these sterile injections [from NECC] for back and joint pain, a procedure that lacks high-quality evidence of efficacy. These problems cannot be laid entirely at the feet of compounders when clinicians persist in clinical practices despite weak evidence of efficacy.”