More than two weeks after the first reports emerged of meningitis cases linked to tainted painkiller injections, health officials at the Centers for Disease Control and Prevention (CDC) say the number of cases will continue to rise, since the infections may take weeks to appear.
CDC officials say that an estimated 14,000 people may have received injections in recent months from three contaminated lots of methylprednisolone acetate, a steroid used to treat back and joint pain. Among those who have been diagnosed with meningitis resulting from the tainted shots, symptoms have arisen anywhere from one to four weeks after their last injection. The symptoms include fever, new or worsening headache and in severe cases, neurological confusion consistent with stroke.
So far, the CDC has confirmed 185 cases of meningitis and 14 deaths in the current outbreak, now reaching 12 states. Meanwhile, a U.S. House of Representatives committee is investigating the company, New England Compounding Center (NECC), that produced the contaminated shots. And a Minnesota woman has filed the first lawsuit against the company.
Initial reports traced the meningitis outbreak to the Aspergillus fungus, which was found in the first case in Tennessee and in a sealed vial of the steroid drug. More recently, however, public health labs in Virginia have reported that another fungus — Exserohilum — may also have contaminated the injections.
Both the Food and Drug Administration (FDA) and the Massachusetts Department of Public Health (DPH) are continuing their investigations of NECC, based in Framingham, Mass., which made and distributed the injections, which were supposed to be sterile. Deborah Autor, deputy commission for global regulatory operations and policy at the FDA, told reporters during a recent teleconference that 50 vials of sealed methylprednisolone acetate collected both at NECC and at hospitals or clinics to which the company had shipped its product tested positive for fungus.
The first case of meningitis linked to the current outbreak was reported in Tennessee in late September. On Sept. 26, the Massachusetts board of pharmacy initiated an inspection of NECC and was joined by the FDA the following week. Two days later, on Oct. 3, NECC voluntarily surrendered its pharmacy registration to the state and no product has been produced at the facility since then. On Oct. 6, the company voluntarily recalled all of is products currently in circulation around the country.
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While the agencies investigate how fungus could have contaminated the sterile process of making the injections, even bigger questions loom about how NECC was allowed to continue operations despite being in violation of licensure from the state of Massachusetts. As a compounding pharmacy, NECC was obligated to make medications only on a patient-by-patient basis, and only when presented with a specific prescription for a particular medication. Common reasons that doctors and hospitals turn to compounding pharmacies for drugs include needing a medication in a different form — in a liquid, for example, when the medication normally comes in pill form. Compounding pharmacies will also be asked to add flavorings to medications for children, or to remove potentially allergenic agents and replace them with alternative ingredients.
But it’s clear that NECC had shipped bulk quantities of methylprednisolone acetateto 23 states, an act that was “in violation of the licensing regulations in our state,” according to Dr. Madeleine Biondolillo, director of DPH’s bureau of health care safety and quality. “The regulatory authority at the Massachusetts board of pharmacy does not include tracking volumes of medications. Our regulations are specific, saying that each dose of medication produced in compounding procedures has to be tied to a patient’s prescription, but nothing speaks to tracking the volume question.”
But because NECC was distributing its products so widely, in 2006, the FDA had sent a warning letter to the company noting that it was in violation of its licensing agreement and pushing the line between compounding and commercial manufacturing. Because compounding pharmacies do not make commercial quantities of drugs, they are not regulated by the FDA; the agency’s authority over compounding pharmacies’ activities is “very, very complicated,” as Autor told reporters during the recent briefing. Compounding pharmacies are regulated by the state boards of pharmacy in the states in which they operate.
The FDA says NECC responded to the warning letter, assuring the agency and the state that it was operating in compliance with regulations and in the best interest of its patients. The company also told the agencies that it was producing sterile products according to compounding practices laid out in the U.S. Pharmacopeia, which sets standards for purity, identity, quality and consistency on how medications are made.
But, said Autor, enforcing these standards is tricky because of ambiguity about which agency has regulatory authority over compounders and how far that authority extends. “The challenge is the lack of clarity in the law. The pharmacy practice and the industry have evolved a lot, and that needs to be taken into account in the future in coming up with an appropriate regulatory scheme.”
As the investigations continue, public health officials say they have reached out to 12,000 of the potentially 14,000 people affected, and urge anyone who has received shots from one of the three tainted lots produced by NECC to contact their physician immediately.