Compounding pharmacies started as small mom-and-pop stores that mixed hard-to-find medications for local doctors and their patients who had allergies, difficulty swallowing, or otherwise could not take mass-produced drugs.
But amid growing drug shortages in the pharmaceutical industry, some large compounders such as the New England Compounding Center stepped in and expanded their business far beyond the industry’s homespun roots.
The Framingham company, whose products are implicated in a nationwide outbreak of fungal meningitis that sickened more people Friday, listed dozens of products online and apparently took thousands of orders from doctors, clinics, and hospitals in at least 23 states, a transformation that regulators have not kept pace with, critics and even some industry executives said.
“A question still has to be answered: Who the heck at the government level was asleep at the switch?’’ said David G. Miller, executive vice president of the International Academy of Compounding Pharmacists.
The outbreak starkly illustrates the yawning gap in oversight, said Allen Vaida, executive vice president of the Institute for Safe Medication Practices, a Pennsylvania-based advocacy and research organization. The US Food and Drug Administration is supposed to regulate compounding companies that ship their products to many providers, a practice known as outsourcing, while state pharmacy boards monitor the small mom-and-pop operations. But the rules are too vague to delineate when a compounder crosses that line, he said.
“The state boards of pharmacies are not equipped financially or with the knowledge to really inspect these types of operations,” Vaida said.
Federal and state health officials are investigating the outbreak of a rare and severe type of meningitis caused by fungus known as aspergillus and exserohilum. The number of people sickened Friday grew to 47 in seven states, including five who died from the infection, which attacks the brain and spinal cord, the US Centers for Disease Control and Prevention reported. Patients with lower back pain received injections of a steroid made by New England Compounding Center. Contaminants injected into the spine can easily travel to the brain.
The CDC and FDA said Friday that the investigation into the cause of the outbreak is ongoing. But the FDA found a sealed vial of the injectable steroid, called methylprednisolone acetate, contaminated with fungus at New England Compounding. The agency is testing the sample further to determine the species of the fungus. Foreign material could easily be seen floating in other vials found at the company, FDA officials said.
Infected patients received drugs from three lots of methylprednisolone acetate, containing 17,676 one-dose vials that the company shipped to providers in 23 states. The CDC listed those 75 providers on its website Friday.
New England Compounding has recalled about 35 products it prepares for injection in and around the spine, according to a list on the FDA website. Federal and state health officials have also urged doctors, clinics, and hospitals to stop using all products made by the company.
Health agencies are imploring caregivers to immediately track down patients who received injections from the three potentially contaminated lots and monitor them for symptoms, including fever, new or worsening headache, nausea, and numbness and slurred speech similar to a stroke.
This is hardly the first time that problems with compounding companies have resulted in widespread infections. At least 33 patients in seven states contracted fungal eye infections from products mixed at a Florida pharmacy, federal officials said in May. And there have been numerous other instances of compounding-related illnesses.
According to Miller, the number of pharmacies that specialize in compounding has grown from 5,000 three years ago to more than 7,500. Of those, 3,000 provide compounding for drugs that need to remain sterile, such as those that are inhaled and injected.
Patient safety advocates have long urged officials to strengthen federal oversight of compounding companies. In testimony before a congressional committee nine years ago, Sarah Sellers, executive director of the Center for Pharmaceutical Safety, said it was ironic that officials were so focused on regulating imported drugs while the country had “within our own borders a flourishing, unregulated [compounding] industry that manufactures, markets, and sells substandard products throughout the US.”
New England Compounding has been investigated by state and federal regulators several times, in some cases for overstepping its bounds as a compounding pharmacy and venturing into manufacturing. The FDA received three complaints about the company in 2002 and 2003 involving its preparation of methylprednisolone acetate, one of the complaints concerned lapses in sterile procedures, leading to investigations by the state and the FDA, said Massachusetts health officials.
A complaint this year about the potency of eye medications remains under investigation.
During an inspection in fall 2004, the FDA found numerous problems at the company, which were detailed in a 2006 warning letter.
The agency said that “like a manufacturer,’’ the company developed an anesthetic drug called Extra Strength Triple Anesthetic cream, for which it generated “sales by giving physicians ‘courtesy prescriptions’ (i.e., free samples). These actions are not consistent with the traditional practice of pharmacy compounding,” the FDA warned. Compounders produce “reasonable quantities of drugs upon receipt of valid prescriptions from licensed practitioners to meet the unique needs of individual patients,’’ the agency said.
Yet, the company apparently continued to ship large orders.
“Based on the quantity and the distribution into 23-plus states, we are struggling as an organization to understand how that volume could have corresponding prescriptions associated with’’ the drugs, Miller said. “The board of pharmacy is supposed to decide if they crossed the line.’’
The company declined to answer questions about its practices Friday.
Rules vary by state, but if compounding pharmacies meet certain conditions, they are allowed to sell to out-of-state providers, said Eric Kastango, a pharmacist and consultant.
But the problem, he said, is that many state inspectors don’t have the expertise the FDA possesses. “They may not understand the nuances and details of sterile compounding operations,’’ said Kastango, who is a member of the United States Pharmacopeial Convention, a nonprofit organization that publishes standards for pharmacies. He said he was not speaking on behalf of the group.
But, Kastango said, the FDA also has struggled with how to regulate compounding pharmacies, which are not held to the same safety standards as the pharmaceutical industry.
The FDA would not comment Friday about regulatory challenges. The Massachusetts Department of Public Health released a statement that said pharmacists and pharmacies are “only permitted to dispense and compound medication pursuant to a prescription from a registered practitioner for an individual patient.”
The department — which oversees the Massachusetts Board of Registration in Pharmacy, the entity that licenses compounders — did not respond to requests from the Globe for an explanation of why New England Compounding had been allowed to ship thousands of vials of medications nationwide, if it was licensed only to prepare medications for individual patients or providers.
The department said in a statement that “all matters concerning [New England Compounding] drug compounding and distribution remain under investigation by federal authorities and [the health department] at this time.”