The nation's growing outbreak of meningitis, linked to spinal injections for back pain, was a calamity waiting to happen the result of a lightly regulated type of drug production that had a troubled past colliding with a popular treatment used by millions of Americans a year.
The outbreak, with five people dead and 30 ill in six states, is thought to have been caused by a steroid drug contaminated by a fungus. The steroid solution was not made by a major drug company but was concocted by a pharmacy in Framingham, Mass., called the New England Compounding Center. Compounding pharmacies make their own drug products, which are not approved by the Food and Drug Administration.
On Monday, federal inspectors at the New England center found a sealed vial of the steroid afloat with so much foreign matter that it could be seen with the naked eye, FDA officials said Thursday.
Under the microscope, the particles were a fungus.
The drug has been recalled, the clinics that used it are scrambling to warn patients who might have been exposed, and health officials are urging anyone feeling ill after a spinal steroid injection to contact a doctor quickly, especially for symptoms like severe headache, fever, nausea, dizziness, loss of balance or slurred speech. They are also urging doctors and hospitals to stop using any products made by the New England Compounding Center.
The pharmacy had shipped 17,676 vials of this potentially contaminated solution to 75 clinics in 23 states, including California, according to Massachusetts and federal health officials.
The question is, why? Why would pain clinics around the country rely on a pharmacy that mixes its own brand of unapproved drugs, especially for a delicate procedure like an epidural injection that has the potential realized in these awful cases to infect a patient's nervous system?
There seems to be no one answer. Some doctors say compounding pharmacies offer specialty products or dosages not easily found elsewhere or sometimes simply better prices than big drug companies.
But other physicians have reservations about using compounded pharmaceuticals.
Dr. Arthur S. Watanabe, an interventional pain specialist in Spokane, Wash., said the steroid for spinal injection was available from mainstream drug companies, and he could not understand why anyone would buy it from a compounding pharmacy.
Compounding has been called an ancient art, something practiced long before medicines were premixed and sealed in bubble packs. The practice goes on today, allowed by states and the federal government, but it is supposed to provide custom-made products for individual patients with special needs. It is frequently done in hospital pharmacies, and an estimated 2 percent to 3 percent of prescriptions in the United States are compounded prescriptions for individual patients, according to the International Academy of Compounding Pharmacists.
Pharmacies and regulators have struggled for years over what limits to set on the practice.
Compounding has fallen between state and federal authorities, and the legal status of compounded drugs has never been clear. Compounding is tolerated by the FDA, as long as the pharmacy does not ship across state lines, mass-produce drugs or use commercial scale equipment, said James H. Ruble, an assistant professor at the University of Utah College of Pharmacy.
But recent court cases, including one in federal court in Florida, have raised questions about the FDA's authority. In a case involving a compound-maker called Franck's that was producing compounds for veterinary use, a judge ruled that the FDA could not assume it had authority to regulate compounding pharmacies, Ruble said. That case is on appeal.
Health officials worry about compounding because it has its risks. The pharmacies are not held to the same safety standards as big drug companies.
The current outbreak is not the first time a steroid made by this type of pharmacy has caused fungal meningitis in people receiving spinal steroid injections. There were five similar cases, including a death, in 2002, all traced to one pharmacy in South Carolina that had been shipping its product to five states. Inspectors found contaminated vials and a complete lack of quality controls or sterility testing at the pharmacy.
In 2011, nine patients at an Alabama hospital died after receiving a feeding solution contaminated with bacteria, which had been prepared by a compounding pharmacy in Birmingham.
The New England center has had a long history of problems. Madeleine Biondolillo, director of the Bureau of Health Care Safety and Quality at the Massachusetts Department of Public Health, said there had been three complaints registered against it in 2002, 2003 and this year in March when the potency of a compound used in eye surgery was questioned. Its ability to perform sterile processing also was questioned. State officials said it made dozens of medications, both injectable and noninjectable medicines, as well as topical creams.
Officials said the center was starting with a powdered drug and mixing it with liquid to make a solution of the steroid methylprednisolone acetate that was ultimately used for spinal steroid injections.
But special care is needed in making drugs to be injected into the spine because of the seriousness of infections there, said Charles Leiter, the president of Leiter's Compounding Pharmacy in San Jose.
"I try and stay away from drugs for the spinal column because if you make a mistake, they are dead," Leiter said. He added, "Taking a suspension and sterilizing it for use in the spinal column is very tricky."
The New England center had also received warnings in the past from the FDA, although not about its steroid drugs. The earlier warnings had cautioned it against opening sterile vials of a cancer drug, Avastin, and repackaging the drug in smaller doses to be used to treat an eye disease. The agency had also warned the center against selling a pain cream that contained a powerful mixture of local anesthetics and that could be toxic and even cause heart problems if too much was rubbed into the skin.
Joe Cabaleiro, executive director of the Pharmacy Compounding Accreditation Board, said that the New England center had never applied for accreditation.