FDA Raced to Find Outbreak Cause

By Walter F. Roche Jr.

A microbiologist for the U.S. Food and Drug Administration testified that he had never seen sterile drugs as contaminated as the ones he rushed to analyze in October of 2012 from the New England Compounding Center.
"I've never seen a sterile product so contaminated," Philip F. Istafanos told jurors.
He said samples of NECC drugs were shuttled from Massachusetts to FDA's National Research Laboratory in Jamaica, New York on Oct. 3 where he and others worked into the night to begin a detailed analysis.
Because of the urgency, the FDA official said staff from New York met counterparts from Massachusetts at the halfway point to collect the samples.
Istafanos was testifying for the prosecution in the trial of Barry J. Cadden, the one time president and part owner of NECC. He has been charged with racketeering and 25 counts of second degree murder. The outbreak sickened some 778 patients across the country, killing 78 of them.
Istefanos said nearly 100 vials of drugs from NECC were brought to his laboratory followed by more than two dozen swabs taken from key locations in NECC's Framingham, Mass. headquarters.
The samples arrived on Oct. 3, just as a formal announcement of the fungal meningitis outbreak was becoming public.
He said a first look at the vials of methylprednisolone acetate showed nine had visible black spots and he removed the stringy mass from one vial to examine it.
"I took out the black material and put it under a microscope," he said, adding that he had never seen anything like what he found in the vials.
He described black threadlike material bundling together, some of which clung to the sides and bottom of vials.
He said half of the samples were sent to the U.S. Centers for Disease Control and Prevention and analysis of the remaining vials began with testing of the dust cover to exclude it as the source of the fungus.
He said they then began testing the actual drugs using three different media or growth agents, instead of the usual two.
Though the full process normally takes 14 days, Istafanos said,"It was urgent. We needed a faster result."
He said they began examining the samples and began to see results in four or five days when a blackish mold became visible. In addition to the mold, analysis showed the presence of yeast, which Istafanos described as a "very unlikely" combination.
"It was contaminated, very contaminated, very bad," he said.
He said 49 of the 50 samples had yeast and mold and one had only yeast.
He said as a control they replicated the testing process with substances known to be sterile. Those produced no growth.
Describing blackish and white-ish mold found in the NECC drugs, Istafanos said, "This is a sterile drug. It should have nothing in it."
He said 11 of the environmental sample swabs also tested positive.
Earlier in the day Roger Edwards, a forensic accountant hired by the FDA, testified that Cadden and his wife collected $19.5 million in salary and profits from NECC between 1998 and the company closing in October of 2012.
Each owned 17.5 percent of the company. Barry Cadden collected $10.9 million in salary and profits while Lisa Cadden collected over $8.6 million.
A third witness, FDA investigator Kristina Donohue, testified about inspections of NECC she conducted in 2002 and 2003. She said the agency had received complaints that even though it was only licensed as a pharmacy, NECC was acting like a drug manufacturer, which would make it subject to stricter FDA regulation.
On her first visit in 2002 she said she observed a beaker of betamethasone covered with tin foil. Calling it "problematic," Donohue said the situation raised concerns about sterility. She said they also noted NECC was not doing end product testing and there were concerns about expiration dates of some products.
She said that when she returned in 2003, the physical size of the NECC operation had doubled and staff had jumped from eight to 12.
She said Cadden told her NECC was issuing drugs only with patient-specific prescriptions, as required by law. She said staff from the Massachusetts Board of Pharmacy accompanied her on the NECC visits because that board licensed the company.
At that point, Donohue said, the FDA considered NECC to be acting as a pharmacy, subject to state regulation and not the stricter FDA standard for drug manufacturers.
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