PHILADELPHIA - By 2003, surgeons trained by a Pennsylvania medical-device company had seen serious complications from an unauthorized test of a bone-cement product.
The cement had been approved to treat broken bones, but not weight-bearing hips and spines. Yet Synthes Inc. officials forged ahead with their own tests, teaching doctors how to use it for fractures in places not approved by federal regulators.
Then, a patient died in the operating room in Plano, Texas. Within months, two more died in surgery in northern California. Even then, no one called the FDA.
In a rare move, U.S. prosecutors are seeking prison time for four top Synthes executives who pleaded guilty last year to misdemeanors as "responsible corporate officers." The closely watched criminal case is playing out this week in Philadelphia, where attorneys for the government and the executives are making their cases before U.S. District Judge Legrome D. Davis. The judge has not yet scheduled individual sentencing dates.
Prosecutors call their crimes intentional and say a Synthes consultant warned early on that the tests amounted to "human experimentation."
The defendants deny any intent to violate U.S. Food and Drug Administration protocols.
A lawyer for former Synthes vice president Richard Bohner argued Tuesday that his client "made repeated good-faith efforts to prevent off-label promotion."
Davis agreed, to a point. But he asked why Bohner didn't do more.
"I think that's a question that he asks himself every day, why he didn't go farther. And that's why he's here," lawyer Brent J. Gurney said.
Prosecutors' push for prison time caught the executives off guard after they entered their pleas in mid-2009. Since then, their sentencings have been stalled amid protracted legal filings and a change in judges. But each man has already lost his job and been fined $100,000.
"It's a conflict between the (corporate) culture and the law that brings us here," Davis said during this week's pre-sentencing hearing, where lawyers have been debating just what each man knew and did. "The intersection here is whether the company's culture, the behavior, exceeded the boundaries of what the FDA would allow."
The defendants are former Synthes North America president Michael D. Huggins, 53, of West Chester; former senior vice president Thomas B. Higgins, 54, of Berwyn; ex-director of regulatory and clinical affairs John J. Walsh, 48, of Coatesville; and Bohner, 57, of Malvern.
The Justice Department in recent years has collected billions of dollars from off-label marketing cases, many of them brought by whistleblowers and filed in Philadelphia, a hub for both pharmaceutical companies and the department's health care fraud efforts.
Both Synthes, a global company that specializes in surgical hardware, and Norian Corp., a subsidiary based in West Chester, pleaded guilty to corporate health care fraud charges last year and agreed to pay the maximum $23 million in fines.
The fines pale compared with the $2.3 billion that Pfizer paid over its promotion of several drugs, or the $1.4 billion paid by Eli Lilly for off-label marketing of the anti-psychotic Zyprexa. But the push for prison time has caught the industry's attention.
Some pharmaceutical-industry lawyers say the line between legal and illegal marketing is not always clear. And Higgins' lawyer, Adam S. Hoffinger, noted Tuesday what he called the "disconnect" between the fact that doctors are free to use products however they wish, while companies cannot promote the alternative uses.
Synthes was eager to expand its sales to the hundreds of thousands of Americans, many elderly, who suffer spine fractures each year. But the process of getting FDA approval for clinical trials is famously slow and expensive.
Instead, Synthes from 2002 to 2004 paid for doctors to travel to seminars in San Diego, Dallas and Charlotte, N.C., to teach them how to inject the bone cement into the spine, prosecutors said. The product, Norian X, was used in about 200 spine surgeries.
Earlier pilot studies had shown the cement could cause blood clots in humans, while pig research suggested such clots could move to the lungs, according to the June 2009 indictment. But with competitors ahead in the race to market, Synthes was eager to move forward, authorities charged.
The patients who died in surgery suffered severe hypotension, or low blood pressure, following the injections. None of the surgeons could rule out the bone cement as a factor in the deaths, but it also wasn't definitively blamed for them. At least one of the patients was already frail and elderly.
According to prosecutors, the defendants not only tested the bone cement on humans, but failed to report the deaths and lied to FDA investigators during a routine 2004 audit.
As part of the corporate pleas, Synthes agreed to sell the Norian subsidiary.