A New England Compounding Center meningitis outbreak that began in September 2012 sickened 798 individuals and resulted in the deaths of 64 people. In September 2012, the Centers for Disease Control and Prevention, in collaboration with state and local health departments and the Food and Drug Administration (FDA), began investigating a multistate outbreak of fungal meningitis and other infections among patients who had received contaminated steroid injections from the New England Compounding Center (NECC) in Framingham, Massachusetts. The NECC was classified as a compounding pharmacy. The traditional role of compounding pharmacies is to make drugs prescribed by doctors for specific patients with needs that can't be met by commercially available drugs.
In October 2012, an investigation of the NECC revealed the company had been in violation of its state license because it had been functioning as a drug manufacturer, producing drugs for broad use rather than filling individual prescriptions. In December 2012, federal prosecutors charged 14 former NECC employees, including president Barry Cadden and pharmacist Glenn Chin, with a host of criminal offenses. It alleged that from 2006 to 2012, NECC knowingly sent out drugs that were mislabeled and unsanitary or contaminated.
In a congressional hearing the FDA Commissioner was asked why regulators at the FDA and the Massachusetts Board of Pharmacy did not take action against the pharmacy years earlier. The legislators were told that the agency was obligated to defer to Massachusetts authorities, who had more direct oversight over pharmacies. The FDA Commissioner also stated, "In light of growing evidence of threats to the public health, the administration urges Congress to strengthen standards for non-traditional compounding." The Drug Quality and Security Act (H.R. 3204, 113th Congress), a bill to grant the FDA more authority to regulate and monitor the manufacturing of compounding drugs, became law on November 27, 2013.
The incident resulted in numerous lawsuits against NECC. In May 2015, a $200 million settlement plan was approved that set aside funds for victims of the outbreak and their families.
Outbreak
In September 2012, an outbreak of fungal meningitis was reported in the United States. The U.S. Centers for Disease Control and Prevention traced the outbreak to fungal contamination in three lots of a medication called methylprednisolone used for epidural steroid injections. The medication was packaged and marketed by the New England Compounding Center (NECC), a compounding pharmacy in Framingham, Massachusetts. Doses from these three lots had been distributed to 75 medical facilities in 23 states, and doses had been administered to about 14,000 patients after May 21 and before September 24, 2012. Patients began reporting symptoms in late August, but, because of the unusual nature of the infection, clinicians did not begin to realize the cases had a common cause until late September. Infections other than meningitis were also associated with this outbreak, which spanned 19 states. As of March 10, 2013, 48 people had died and 720 were being treated for persistent fungal infections. This page is updated weekly, but it links to all earlier versions. In November 2012, some patients recovering from meningitis were reported to be experiencing secondary infections at the injection site. Although no cases of infection were reported to be associated with any other lots of medication, all lots of all medications distributed by NECC were recalled in separate actions by NECC and regulators. Subsequent analysis identified some contamination in other lots.
On October 9, 2012, members of the United States Congress asked federal health officials for briefings on the outbreak as a first step toward possible legislative action to strengthen federal drug safety regulations. On November 14, 2012, members of a congressional committee investigating the outbreak accused the Food and Drug Administration (FDA) of failing to prevent the crisis by moving too slowly against the Massachusetts pharmacy. FDA commissioner Margret Hamburg testified that the agency's efforts to address problems at the compounding center had been hamstrung by Congressional interference, conflicting court rulings regarding FDA jurisdiction, and tenacious litigation by the compounding center itself. At the same hearing, the co-owner of NECC chose to plead the Fifth, refusing to answer all questions. By mid-December, over 400 lawsuits had been filed against NECC.
In October 2012, Massachusetts shut down two more compounding pharmacies over sterility concerns after they conducted a surprise inspection. In December, unexpected inspections of three more Massachusetts pharmacies found problems as well.
On December 21, 2012, the New England Compounding Center filed for Chapter 11 bankruptcy protection in the Massachusetts district bankruptcy court.
On September 4, 2014, pharmacist Glenn Adam Chin was arrested at Boston's Logan International Airport before boarding a plane headed to Hong Kong, and was charged with one count of mail fraud. Chin was responsible for supervising the clean rooms at the NECC and was involved in compounding the contaminated methylprednisolone. The FDA affidavit stated that Chin had used improper sterilization and testing techniques, unsafe practices, falsified cleaning logs, and ordered pharmacy technicians to fraudulently mislabel vials. Chin was the first to be charged in the ongoing inquiry.
On December 17, 2014, 14 former NECC executives and technicians, including co-founder and president Barry Cadden, were indicted on a host of federal charges related to the outbreak. Most seriously, Cadden and Chin were charged with helping orchestrate a massive racketeering conspiracy that led directly to 25 of the deaths.Bidgood, Jess; Tavernise, Sabrina. Massachusetts Pharmacy Owners Arrested in Meningitis Deaths. New York Times, 2014-12-18.
Source of infectious agents The Centers for Disease Control and Prevention (CDC) traced the outbreak to contaminated methylprednisolone (MPA) used for epidural steroid injections."Frequently Asked Questions for Clinicians: Multistate Outbreak of Fungal Meningitis and Other Infections" . Centers for Disease Control and Prevention (CDC). The Food and Drug Administration (FDA) examined foreign materials from unopened vials under microscope and found fungal matter. The fungus was found in the cerebrospinal fluid of several patients, which confirmed fungus caused the meningitis. The medication was packaged and marketed by the New England Compounding Center (NECC) of Framingham, Massachusetts.
According to the CDC, between May 21 and September 24, 2012, patients in 23 U.S. states received injections from three implicated lots of a steroid, preservative-free methylprednisolone acetate, for back pain, and some of these patients developed symptoms consistent with fungal meningitis. This form of meningitis can be caused by epidurally administered medications, but is not contagious by person-to-person contact. On October 9, authorities estimated as many as 14,000 patients may have been exposed to the contaminated drug.
The NECC said that immediately after it was notified about the infections it initiated a voluntary recall September 26. Next, on October 4, the Massachusetts Department of Public Health issued a recall of all NECC medications, advising hospitals and clinics to remove and segregate all lots from their stock inventory.Commonwealth of Massachusetts Board of Pharmacy - New England Compounding Center recall notice October 4, 2012 NECC also announced on that day they were suspending all of their operations and voluntarily surrendered their licenses to the Massachusetts Department of Health and Human Services, while continuing to cooperate with the ongoing investigations by the CDC and the FDA.
On October 15, the FDA issued a warning that two more drugs may have been contaminated. Both came from NECC. One was a steroid called triamcinolone acetonide and another was a product used during heart surgery. If injected, the second steroid may cause fungal meningitis, while the heart drug may cause a different fungal infection.
Infectious agents
As of November 15, the CDC reported that 85 patients had laboratory-confirmed fungal infections. A black mold called Exserohilum rostratum was found in 84 of the cases and Aspergillus fumigatus was found in one case. Other fungi were found in eight cases, but were not known to be significant. According to specialists in fungal diseases, cases of meningitis caused by Aspergillus are rare, but cases caused by black mold are even more so, making the discovery of the outbreak and the recommended treatment almost entirely untrodden medical ground.
Aspergillus is a common mold genus that humans and animals are continually breathing, but that rarely causes problems. However, in patients with suppressed immune systems, or if introduced directly into the spinal column, the fungus can be deadly. Despite the availability of antifungal agents, aspergillosis in the central nervous system carries a poor prognosis. Though this case sparked the nationwide investigation, as of November 4, the CDC said A. fumigatus had been identified in only one patient. Almost all cases in the outbreak involved a different fungus, Exserohilum rostratum, another common mold that rarely causes problems.
Clinical features On October 12, 2012, the CDC reported that as of that date, the median age of the patients was 68 years (range: 23–91 years); 48 (69%) were female. At presentation, 57 (81%) had headache, 24 (34%) had fever, 21 (30%) had nausea, and seven (10%) had photophobia (intolerance to bright light). Atypical neurologic symptoms were observed in a minority of patients, subtle gait disturbances were seen in three (4%), and a history of falls was described in eight (11%). Meningeal signs, including nuchal rigidity (the inability to flex the neck forward), Kernig's sign, or Brudzinski's sign, were uncommon, occurring in 10 (14%) patients. Stroke, either as a presenting sign, or as a complication of infection, occurred in 12 (17%).
According to the CDC report, for 61 people with symptom onset date available, the earliest date was August 18. For the 48 patients with both injection date and symptom onset date available for analysis, the median time from last steroid injection to onset of symptoms was 15 days (range: 1–42). A total of 25 of the 48 patients received a single steroid injection; the median time from injection to onset of symptoms for those patients was 16 days (range: 4–42). People who received injections were most vulnerable to stroke and infection within the first 42 days of injection, but three months may be needed for symptoms to appear.
Fungal infections associated with nonepidural injections were also reported. They were related to injections in a peripheral joint space, such as a knee, shoulder, or ankle. People injected in peripheral joints were at risk for joint infections but were not believed to be at risk for meningitis.
On November 4, some people who were treated for meningitis and released returned to the hospital with abscesses, a localized infection of the tissues at the injection site, that could lead to meningitis. The deputy chief of the mycotic diseases branch of the CDC said, "We don't have a good handle on how many people are coming back. We are just learning about this and trying to assess how best to manage these patients. They're very complicated." As of December 7, spinal abscesses had been reported in 23 patients who received injections in Tennessee, and 37 patients in Michigan.
The CDC reported that doctors were also reporting that some people that had been injected with the contaminated drugs had arachnoiditis, a nerve inflammation that can cause intense pain, bladder problems, and numbness.