Tainted Syringes Slipped Past FDA’s Watch
Natalie Fullerton's parents were thrilled to watch their year-old daughter bounce back from a double-lung transplant. Within months, she was mimicking her sister's ballet poses and gleefully repeating the word "purple."
Her father, Leslie, carefully tended to Natalie, following an intricate regimen to keep her healthy. After doctors implanted a tube in Natalie's chest to give her intravenous medication, he dutifully used fluid-filled syringes to clean it.
Days later, the 29-month-old was back in a Texas hospital, breathless and feverish. Bacteria had infected her blood, the first in a cascade of complications over four months. In the end, Natalie died in her mother's arms.
Leslie Fullerton can't shed his sense of guilt. "I'm the one who killed my daughter," he said.
But there is mounting evidence the blame lies elsewhere.
The syringe Fullerton used was part of a contaminated lot that since has been linked to at least 4 deaths and 162 illnesses nationwide. And records show that the Food and Drug Administration missed several chances to stop the syringes from getting out.
Update (June 6, 2009 - 11:45 AM): This story has been updated with the FDA's response. Jump to the updated paragraph.
Three months before the pre-filled syringes were shipped in October 2007, an FDA inspector visited the plant in North Carolina where they were made. She investigated reports of red, brown and black particles in syringes and reported that managers had a plan to deal with rust.
The inspector did not note that the plant had switched to an unreliable sterilization method.
A week later, when the FDA learned a distributor was recalling 1.3 million of the syringes, the agency should have launched a thorough inspection, according to its operations manual. That didn't happen, an FDA spokeswoman now says, because the agency is so understaffed it no longer follows the policy unless the recalled product posed a reasonable probability of serious injuries or deaths.
Finally, after reports of harm in late 2007, FDA inspectors combed the plant, called AM2PAT. They discovered a "gummy brown" substance on the syringe-filling machine and brown water flowing from taps, among other problems. The plant was closed in January 2008.
Federal prosecutors zeroed in on AM2PAT's President, Dushyant Patel, who lived in Chicago's northwest suburbs but commuted to operate AM2PAT. An indictment on fraud, conspiracy and other charges alleges that his firm lied about performing sterility tests and produced pre-filled syringes laced with bacteria.
Patel fled the country as investigators closed in, evading charges that could bring 95 years in prison. Two employees, including a Carpentersville, Ill. man who was the plant manager, were sentenced in February to 4 ½ years in prison for fraud and for allowing tainted drugs into the marketplace.
Too little, too late for sickened patients
The syringe case has not received the attention that followed deaths this year from salmonella-laden peanut paste, another instance in which the FDA was criticized for acting slowly. Consumer advocates and experts who follow the FDA say both safety breakdowns are the predictable result of a long-term shift from aggressive enforcement to "partnership" with the industries it oversees.
"That tells me if the cop leaves the beat, the bad guys feel that they can do what they want to do," said William Hubbard, a former FDA associate commissioner and consultant to the advocacy group Alliance for a Stronger FDA.
For this article, Gordon Harnack, a consultant who helps medical device companies prepare for inspections, reviewed more than 120 pages of FDA reports on the AM2PAT plant dating to 2005. He said inspectors didn't look deep enough, and FDA managers were too tolerant.
"Time after time, the evidence was there that [AM2PAT] management had little intent of complying with adequate FDA regulations," Harnack said. "In 2005, [the FDA] might have caught it. In 2007, they should have caught it. And finally when reports of deaths came in, it all became evident."
“This incident underscores my belief that it is critically important for the FDA to take an aggressive approach to inspections and maintain vigilance in ensuring that manufacturers fully comply with their regulatory, legal and moral obligations to ensure that the products they produce for the American people are safe and effective,” Hamburg said in a statement.
Earlier, FDA spokeswoman Siobhan DeLancey had defended the agency's actions, saying inspectors visited the AM2PAT plant multiple times over several years on a "relatively low number of complaints." Once reports of infections came in, the agency worked hard to help prosecute the two plant managers, she said.
But that's too late for the Fullertons and other families who link the syringes to death or illness, many of whom have filed lawsuits against AM2PAT. In their suit, the Fullertons claim that an AM2PAT syringe compromised Natalie's health and led to her death.
Jim Tallian is among them. The suburban Chicago man blames AM2PAT for an infection that set back his recovery from a blood condition that often leads to leukemia.
Tallian had received a stem cell transplant when an AM2PAT syringe was used to flush a catheter in his chest on Dec. 3, 2007, according to his lawsuit. He contracted a bloodstream infection and was treated in Rush University Medical Center for four days.
"I was shaking so bad it was like I was having convulsions," he said. "I couldn't stop."
Unaware his syringes might be contaminated, he had his catheter flushed again the day after he was discharged. Tallian fell ill a second time and had to be rushed to the emergency room.
"I was in a very vulnerable situation because I had just gotten out of the hospital after my transplant," said Tallian, who is married with three children. "After three weeks of chemotherapy, anything could take you out."
Complaint cites "white whispy" material
Dushyant Patel, a former pharmacist, bought a share of the North Carolina business in 2001 and took over the top job. He lived with his wife and two children on a cul-de-sac in the Chicago suburb of Lake Zurich, where neighbors describe him as friendly but constantly working and regularly out of town.
Prosecutors claim Patel's operation was a fraud from the start, saying the firm's application to make syringes included fake data for a test to establish their shelf life. Apparently unaware, the FDA gave Patel the go-ahead to start production in late 2003.
The firm bought empty syringes and filled them with saline or the blood thinner heparin, solutions that prevent clots from forming in catheters used to deliver medicine directly into a vein.
AM2PAT sold its syringes to distributors that marketed them to hospitals and pharmacies. The factory earned nearly $7 million in profits during its final two years, according to prosecutors.
The federal indictment accuses Patel of doctoring records at the factory and putting "adulterated" drugs into the marketplace. Authorities believe he is in his native India and are seeking to extradite him.
The plant, located in a former strip mall in Raleigh, initially didn't attract much FDA scrutiny. Then, in March 2005, a pharmacist reported finding "copious" amounts of orange sediment floating in an AM2PAT syringe, FDA records show. He saw an inch-long black hair suspended in another.
An FDA inspector arrived at the plant in June 2005 and spent six days, much of it at Patel's side. She watched a worker fill a syringe while chewing gum and saw others inspecting syringes at a conveyor that was moving too fast.
She noted nine "significant" violations, records show, some of which could have "an adverse effect on product quality."
Soon after, the FDA sent a warning letter requiring AM2PAT to correct the problems. Then, after another visit in January 2006, the FDA said Patel had either fixed or promised to address the major concerns.
In the spring and summer of 2007, a patient's relative and medical workers lodged new complaints with the FDA. "White wispy" material floated in one syringe, according to the FDA complaint. A patient with a bloodstream infection saw brown particles in another syringe from the same batch. An AM2PAT worker claimed management "was not adhering to the appropriate clean room temperature during manufacturing."
The FDA's Atlanta branch scheduled an inspection for June 26, 2007. But when the inspector arrived in Raleigh, the plant was shuttered.
By the time an inspector tracked AM2PAT to a new site, 30 miles south in Angier, one of the plant's distributors had taken action based on other complaints.
B. Braun Medical, of Bethlehem, Pa., told customers on July 30 that it was recalling more than a million syringes following reports of particles floating in the saline. FDA policies don't set a deadline for companies to report a recall, and the agency didn't learn of B. Braun's action until a week later, spokeswoman DeLancey said.
Unaware of the recall, the inspector focused on other reports of particles in the syringes. She walked through the plant and reported that managers had a plan to deal with rust contamination. Her final report centered on another problem: Workers weren't putting the company name or address on syringes, making them hard to trace.
Six weeks after the August inspection, the FDA issued a news release on the B. Braun recall. The particles were medical-grade silicone, the agency said, and were capable of causing brain damage or a deadly clot.
The FDA now acknowledges that until reports of contamination-related injuries mounted, its Philadelphia office did not pass along information about the recall to its Atlanta branch. That office managed AM2PAT inspections and knew the plant's history. "It was a lapse in communication," DeLancey said.
Records mask sterility shortcuts
Toward the end of October 2007, the plant shipped heparin-filled syringes contaminated with bacteria, authorities say, and patients who used them soon started arriving at hospitals from Florida to Nebraska, some more than once.
Scores fell ill. Health authorities now link four deaths to the contamination, but due to patient privacy laws, it is unclear whether they include Fullerton in that tally. The family's civil suit still is pending.
After the Centers for Disease Control linked sick patients to the syringes on Dec. 11, 2007, two FDA investigators and a microbiologist arrived at the factory. Over two weeks, they interviewed workers, dug through records, examined equipment and studied quality control.
Inspectors learned Patel had concluded—for reasons the company was unable to document—that a standard sterilization process involving radiation had failed, giving rise to the white particles that spurred the recall. Patel then adopted "UV light" sterilization, which the FDA called a "novel, nontraditional" technique.
An employee also told investigators that for six months workers at the plant had been rushing syringes out the door before completing sterility tests.
To cover up the practice, the criminal indictment alleges, the company kept two sets of records—one revealing the rushed shipments and another stating falsely that the plant was holding syringes on site for 14 days while chemists conducted sterility tests.
When confronted with the duplicate paperwork, Patel said someone was "sabotaging" his records, according to the FDA's account.
Investigators snapped photos of workers in plastic patio chairs in front of a towering mound of syringes to be inspected. Box fans held together with duct tape circulated air in a room that was supposed to be outfitted with sterile equipment.
The photos are part of the case against Patel built by George Holding, the U.S. attorney prosecuting the case.
"If you show these pictures to someone,'' he said, "and ask if this is a high-tech biotech company operating in the United State of America, a lot of people would say, ‘No way.' "
Harnack, the industry consultant, said the inspector should have delved deeper, knowing the company violated FDA regulations by not reporting its move to Angier. She should have made sure AM2PAT re-evaluated its equipment and, given a report of contamination, pulled samples for testing, he said.
Back in the Chicago area, Patel's wife and children apparently still live in their suburban home, but she did not respond to requests for comment. In a brief interview, his younger brother said he last heard from Patel 1½ years ago and was worried.
"He's the nicest person, the most brilliant mind," said Mehul Patel, who lives in Texas. "I don't know when something went wrong."
Deborah L. Shelton is a reporter with the Chicago Tribune. ProPublica researcher Lisa Schwartz contributed to this story.