The account describes the same problems at the heart of the ongoing scandal — the contamination of medicines and the mass production of supposedly custom-made substances. It also sketches a portrait of one of the owners, businessman Barry J. Cadden, who benefited from the regulatory murkiness governing his industry.
Problems began in March 2002 when the FDA learned of two patients who developed symptoms suggestive of septic shock after being injected near the spine with a painkiller, betamethasone.
The drug was made by NECC. In all, five people became ill. FDA sent inspectors to NECC’s workrooms in Framingham, Mass. On the first day of the inspection, according to the narrative, “Mr. Cadden was cooperative.” On the second day, however, he “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.”
The inspectors were interested in a particular numbered lot of the steroid, but Cadden “stated that he did not believe betamethasone was ever compounded for that lot number.” However, the investigators contacted the health-care professional who had reported the illnesses; that person told them that not only had he returned drugs from the suspect lot but also “had spoken by telephone to Mr. Cadden about the incident.”
Soon after, according to the narrative, the FDA and Massachusetts Board of Pharmacy inspectors learned that “about four lots” of betamethasone sent by NECC to an outside lab tested positive for endotoxin, which is evidence of bacterial contamination. In the meantime, Cadden had figured out the source of the contamination and changed his production method.
On April 6, he made a new batch of betamethasone and sent a sample to the outside lab for testing, which would take about a week. He kept the rest of the batch in a beaker covered with aluminum foil inside a ventilated hood.
When they saw this, the FDA inspectors “discussed with Mr. Cadden that this was not an acceptable process for maintaining sterility. . . . Mr. Cadden stated he didn’t want to waste the money on vials or the effort . . . if the lot failed testing,” according to the FDA report quoted in the narrative.
When the tests came back clean, Cadden bottled the rest of the batch in vials. When an FDA inspector suggested he test those, too, Cadden agreed. Those tests apparently also came back clean. However, during an exit interview with the inspectors, Cadden said the beaker capped with foil “didn’t contain the betamethasone.”
In response to these problems, the state pharmacy board filed complaints against NECC and Cadden. The company made changes and in February 2004 passed an inspection by the state. In the meantime, however, the FDA was looking into new reports of infection linked to NECC-made steroids.
Two people in Rochester, N.Y., had developed bacterial meningitis after being injected with methylprednisolone acetate — the same drug implicated in the current outbreak. FDA’s New York district office sampled 14 vials provided by the hospital in Rochester. Four tested positive for bacteria.
Although NECC often cooperated with authorities, it was surprisingly defiant at times, too.
In an inspection in late 2004 involving questions about NECC’s production of a dye called Trypan blue, state and FDA inspectors attempted to interview Gregory Conigliaro, who co-owns the company. According to the FDA report, Conigliaro “became indignant [and] he said that he does not really have time to sit with us [and] answer all those questions.” Cadden then told his partner: “Don’t answer any more questions!”
In the same investigation, an FDA inspector asked Cadden whether he had any Trypan blue in stock. Cadden reportedly said “no, because he just compounds the drug if he receives the prescriptions for certain patients.” In the clean room, however, the inspector saw a drawer labeled “Trypan Blue” and asked Cadden to open it. It contained 189 vials of the dye.
The FDA ultimately deferred to the state pharmacy board to make Cadden clean up his operation. That’s because, despite evidence of small-scale mass production at the Framingham plant, FDA concluded that NECC was a compounder, not a drug manufacturer, and, therefore, fell under state regulations.
In a separate development, FDA inspectors found more than a dozen sterility problems at Ameridose, a sister drugmaking facility of which Cadden is also a co-owner.
According to a report released Monday, inspectors found that Ameridose repeatedly failed to perform adequate sterility tests, to investigate more than 53 instances of microbiological contamination in pain medications, and to clean bacteria and mold found in its equipment. A company spokesman said Ameridose has not had “any instance of contaminated products” over the past six years and was preparing a full response to the FDA’s report.
Both NECC and Ameridose have closed in. Cadden’s attorney, Bruce Singal, did not respond to a telephone call and e-mail request for comment.
Lena H. Sun contributed to this report.