Pharmacist Barry Cadden, co-owner of the Framingham pharmacy blamed for the deadly national meningitis outbreak, has a long history of not cooperating with federal regulators, including one 2004 inspection when he initially denied having an eye medication that was the subject of a complaint, according to a memo released Monday by a congressional committee.
An inspector later spotted a drawer labeled with the drug’s name, Trypan blue, and asked Cadden to open it. Inside were 189 vials.
The memo, based on documents and briefings from the US Food and Drug Administration, was prepared by the Republican staff of a House committee holding a hearing Wednesday on the causes of the outbreak and whether it could have been prevented.
They raise questions about why the Massachusetts pharmacy board did not take stronger action against New England Compounding Center, despite having investigated 12 complaints about the company’s practices over a decade and receiving a 2003 warning from the FDA that the pharmacy’s practices could cause “serious public health consequences’’ and should be curtailed.
Staffers of the Oversight and Investigations Subcommittee of the House Committee on Energy and Commerce also questioned why the FDA itself did not take enforcement action against the pharmacy, especially because some of the complaints involved patients becoming ill from New England Compounding products that were supposed to be sterile but were apparently contaminated with microbes. One of those drugs, methylprednisolone acetate, is the same steroid implicated in the ongoing outbreak.
So far, the crisis has sickened 438 people and killed 32 who contracted a rare form of fungal meningitis from a contaminated steroid made by the pharmacy. The committee has subpoenaed Cadden to testify because he indicated he would not appear voluntarily.
Pharmacy spokesman Andrew Paven said he could not comment on the memo, which cites several instances when Cadden refused to cooperate with investigators and challenged the agency’s authority over his business.
NECC ‘disregarded sterility tests, prepared medicine in unsanitary conditions and violated their pharmacy license.’
During an inspection in March 2002, Cadden cooperated the first day but then on the second day “had a complete change in attitude [and] basically would not provide any additional information either by responding to questions or providing records. Mr. Cadden challenged FDA jurisdiction/authority to be at his pharmacy,” according to the memo, which cited an FDA report.
In an FDA inspection report in February 2003, “FDA’s primary NECC investigator and her supervisor recommended that ‘the firm be prohibited from manufacturing until they can demonstrate ability to make product reproducibly and dependably,’ ” the memo said. “They further noted that if the State was unwilling to take action, [they] recommend[ed the] firm be enjoined for GMP deficiencies,” an apparent reference to the agency’s so-called good manufacturing practices.
In a foreshadowing of the current outbreak, the FDA concluded a meeting with state officials on Feb. 5, 2003, by “emphasizing the potential for serious public health consequences if NECC’s compounding practices, in particular those relating to sterile products, are not improved.” Sterile products include injectable drugs and intravenous solutions.
Cadden later responded to the FDA in writing, saying that he had improved his compounding procedures but that his company was not subject to good manufacturing practices because it was a compounding pharmacy not a manufacturer. A compounding pharmacy is supposed to prepare drugs customized for individual patients, such as in doses or forms unavailable from manufacturers. The FDA apparently conceded this point, saying during a meeting that month that it considered the company a compounding pharmacy at that time, leaving ultimate regulatory authority to the state.
The state, however, never took action to stop the company from making drugs, even though it later produced drugs in batches and shipped them to most states — like a manufacturer. In 2004, the state Board of Registration in Pharmacy voted to reprimand Cadden and the company and place both on three years probation, but for reasons that remain unexplained, these actions were not included in a final consent agreement reached with the company in 2006.
“It is clear that NECC knowingly disregarded sterility tests, prepared medicine in unsanitary conditions, and violated their pharmacy license,” Dr. Lauren Smith, interim commissioner of the Massachusetts Department of Public Health, said in a statement Monday. “Poor judgment, missed opportunities, and a lack of appropriate oversight allowed NECC to continue on this troubling path.”
Smith noted that “the board staff who are responsible” have been removed. James D. Coffey, the board’s director, was fired last week, and the board’s attorney was placed on leave.
One week after the inspection in September 2004, during which investigators found Trypan blue in the drawer, FDA investigators had another tense encounter with Cadden and his brother-in-law Gregory Conigliaro, a co-owner of New England Compounding Center, according to the staffers’ memo.
When an investigator asked Conigliaro why the pharmacy was making the eye medication, even though it was not an FDA-approved product, “he became indignant [and] he said that he does not really have the time to sit with us [and] answer all those questions,” the investigator wrote in his report. Cadden told his brother-in-law, “Don’t answer any more questions!”
In a related development Monday, the FDA released a report detailing 15 problems that inspectors found during an investigation at Ameridose — New England Compounding’s sister company and a major supplier to hospitals — ranging from insufficient testing of the sterility and potency of drugs to the presence of insects and a bird in an area where sterile products were packaged and stored.
US Representative Edward J. Markey, a Massachusetts Democrat and a member of the oversight and investigations subcommittee, said in a statement yesterday that the “shared ownership of NECC and Ameridose resulted in shared disregard for basic safety and sterility procedures for manufacturing drugs. Barry Cadden will have much to answer for when he appears before Congress this week at hearings, and I plan to ask state and federal authorities how these companies were able to fall through regulatory cracks and serious violations go unaddressed.”
Officials from the Centers for Disease Control and Prevention said they do not know when the outbreak will abate.
None of the fungal meningitis cases has taken longer than six weeks, from the time of injection, to diagnose. Last Wednesday marked six weeks from the day drugs produced at the Framingham pharmacy were recalled and public health officials began collecting products left over. But public health officials said they are not ready to declare the danger past. “We don’t know the ultimate incubation period, so anyone that received an injection should continue to be vigilant,” said CDC spokesman Curtis Allen.