Federal and Massachusetts officials said Thursday that they lacked clear authority to take action earlier against a now-shuttered specialty pharmacy that set off safety alarms at least six years ago and is now at the center of a burgeoning meningitis outbreak.
In a teleconference with reporters, the officials described a murky, archaic regulatory apparatus that hampered their ability to keep pace with the rapid changes in compounding pharmacies. That industry, which traditionally has consisted of mom-and-pop operations making customized medicines for individual patients, has expanded to include high-volume pharmacies that rival the production of drug manufacturers.
Deborah M. Autor, deputy Food and Drug Administration commissioner for global operations and policy, said it was “really unfortunate that it sometimes takes a tragedy” to bring about change and called on industry officials and lawmakers to adopt a new “regulatory scheme that appropriately controls the risk.” She also said the company could face criminal prosecution.
The officials were responding to questions about why state and federal authorities didn’t move more aggressively against New England Compounding Center in Framingham, Mass., after the FDA found problems during an inspection in 2006. Massachusetts Attorney General Martha Coakley announced an investigation of the NECC after state health officials said the company appeared to violate state licensing requirements.
Fourteen people have died and 170 have been infected from batches of steroid injections contaminated with fungus that were made by the NECC. About 14,000 people received the injections, though it’s not clear how many of those shots were tainted, Centers for Disease Control and Prevention officials said. Some lawmakers already are calling for a criminal probe and new authority for the FDA as a result of the outbreak.
The CDC officials also reported the first infection in a joint — an ankle — that may have been caused by the tainted medicine. More cases of both types of infection are expected.
Fungus causing human disease is notoriously slow to grow and hard to identify. Thirteen cases have been caused by a fungus of the genus Exserohilum and one by the genus Aspergillus. Fungus has been detected in about 50 vials from the company and from clinics that got the product.
J. Todd Weber, the CDC physician leading the investigation of the outbreak, said these are the first meningitis cases caused by Exserohilum ever reported.
The infections have occurred in 11 of the 23 states that got potentially contaminated methylprednisolone acetate from NECC. The medicine is a high-potency, long-acting steroid used to suppress inflammation and relieve pain in people with herniated disks and certain types of arthritis.
The CDC recommendations for treatment of the fungal infection call for two drugs that have to be given intravenously for months. Weber said the drugs are “very strong and can be very difficult for patients to tolerate.”
In 1997, legislation was enacted spelling out the roles of the state and federal governments in regulating compounding pharmacies. But the federal role faced court challenges. As a result, it’s “a murky area,” former FDA commissioner David A. Kessler said.
Other former FDA officials said the agency has sufficient authority over the compounding pharmacies.
“They have all the regulatory authority they need,” said Peter Barton Hutt, a former FDA chief counsel who is now a senior counsel with the law firm Covington & Burling. “They couldn’t ask for any more. What they need are better resources and better coordination.”
He argued that the NECC case was less a result of inadequate authority and more of ineffective communication between state and federal regulators. “Both of them were aware of the problem and neither followed up to make sure the problem was solved,” he said. “Clearly something went wrong there.”
Mary K. Pendergast, who was FDA deputy commissioner from 1990 to 1998, said the agency barely has enough resources to inspect large pharmaceutical plants. “There’s a legitimate worry of spreading resources too thinly,” she said.
As a result, she said, “They play Whac-a-Mole with compounding. If there’s a problem, they whack at it. That’s not necessarily an irrational approach when you consider the bigger problems they’re dealing with.”
Federal and state officials said that the day-to-day operations of compounding pharmacies are governed by state boards of pharmacy. When it comes to FDA authority over compounding pharmacies, much depends on the quantity and type of products.
The agency has long known that compounded drugs can pose safety risks. A 2006 agency survey found that one-third of the compounded drugs sampled had problems, including contamination and incorrect strengths. From 1990 to 2005, the agency learned of at least 240 serious illnesses and deaths associated with improperly compounded products.
Still, the agency has traditionally not taken enforcement action against pharmacies engaging in traditional small-scale compounding, such as making medications for individual customers who are allergic to specific ingredients or preparing medications for children who may be unable to swallow pills or need diluted dosages.
But the agency signaled, in guidance issued in 2002, that it could take action when a pharmacy’s activities raise “the kinds of concerns normally associated with a drug manufacturer.”
The FDA said it could consider action if compounding pharmacies’ drugs were essentially copies of commercially available products, for example, or if the companies were making drugs before receiving specific prescriptions.
“If the question is, could the FDA regulate this type of facility if it produces any large-scale productions? The answer, of course, is yes,” said Boston University’s Kevin Outterson. “But does the FDA know which, out of a couple thousand facilities that are compounding pharmacies, which ones are doing that? Do they have a mechanism to force them to register? That’s not so clear.”
Even given all the uncertainty in the law, “if there is clear evidence that a pharmacy is acting like a manufacturer and in a dangerous manner, there is no question that the FDA has authority to move,” said Jonathan Berman, a lawyer at Jones Day who works on FDA matters.
In fact, the FDA sent the NECC two warning letters in 2006 about potential safety problems with its products. In one, the NECC and four other firms were warned to stop compounding and distributing topical anesthetic creams marketed for general distribution rather than for individual patients.
In the second instance, the FDA and state investigators inspected the plant and found numerous problems. The NECC was making two products — an eye solution and another medicine — that were commercially available. The firm was also promoting an anesthetic cream by giving physicians free samples, much like a drug manufacturer.
The agency was also investigating complaints that the company was repackaging an FDA-approved injectable drug for cancer, Avastin, into syringes for subsequent promotion and sale to ophthalmologists, according to the warning letter. Opening any sterile container immediately compromises sterility, the agency said
The agency also said it had been informed that the NECC, while it requires individual prescriptions for drugs, had told doctors they could use a staff member’s name on the prescription.
Andrew Paven, a spokesman for the NECC, said this week that the company “had resolved its differences” with the agency but did not provide details. The FDA’s Autor said the agency and the NECC exchanged correspondence, and the company assured regulators that it is protecting patient safety.
State officials also said they had no complaints about the company until 2011, and that was related to a physical expansion. The state received a complaint in March that is under investigation, they said.