A cure worse than the disease
When FDA oversight falters, tissue implants can do more harm than good
Five years ago, Warren King, a sports physician, reconstructed the right knee of a patient using a tendon sent to him by CryoLife, a Georgia-based company. The patient quickly developed an infection so serious the implant had to be removed. Tests showed the implant, obtained from a cadaver, had caused the infection. But CryoLife, one of many so-called tissue banks, denied it. "They denied it even when the evidence was overwhelming," King says. The logical step would have been for King to go to the authorities, but he wasn't sure who that would be. "I didn't know the Food and Drug Administration was involved in regulating tissue banks," he says.
Well, the FDA is involved--sort of. Last month the FDA asserted its authority by shutting down most of CryoLife's human-tissue business. And since then, CryoLife has faced ever increasing troubles. Patients who received implants have sued. The Securities and Exchange Commission began investigating the company for possible accounting and insider-trading irregularities, following lawsuits by shareholders who claim that CryoLife misstated the extent of its problems. Company stock has plummeted from a high of $45 a share to as low as $1.40. At week's end, CryoLife said it had been allowed to resume shipment of some tissue products. Still, the company laid off 105 workers, and those who are left are scared of losing their jobs. "It has devastated everybody," one employee says.
But for some patients, the FDA's action is too little, too late. Alan Minvielle of Santa Cruz, Calif., had knee surgery in April 2001 with a CryoLife implant. He developed an infection that ate away so much of his knee, he recently had to have the whole joint replaced. And it wasn't soon enough to save 23-year-old Brian Lykins of St. Cloud, Minn., who died last November after the infection from his knee surgery caused heart failure. "Is the FDA late?" King asks. "There's no question about it."
Unexamined. In fact, a closer look by U.S. News shows that despite FDA oversight, the fast-growing tissue-bank industry has largely gone unscrutinized. The FDA often does not know when companies distribute contaminated tissue. It doesn't approve facilities before companies begin selling products, and it hasn't set requirements on how to treat tissue implants before transplantation. Until recently, it didn't even know the names of all the tissue banks in operation in the United States. Indeed, an industry-sponsored organization--not the FDA--has set the standards for how tissue banks manage their day-to-day operations.
Moreover, although infections pose the greatest risk when a patient receives a tissue implant, the FDA does not require companies to report when they occur. Lacking a centralized database, it is difficult for health officials to spot a cluster of infections coming from one company and thus stop the company from releasing contaminated tissue. It took the FDA at least five months, for instance, to learn that tissue from the South Texas Blood and Tissue Center in San Antonio, which distributed tissue in Texas and California, had infected a patient in late 2000 with E. coli. The agency also realized that the company had taken some of the tissue from the infected donor off the market, but not all of it. The FDA demanded that the tissue bank withdraw the rest of the tissue.
Ironically, it was fear about transmission of infectious diseases that initially got the FDA interested in the tissue-bank industry. In the early 1990s, HIV was spread through organ and tissue donations to transplant recipients. FDA inspectors also found that tissue from foreign countries that had not been screened for diseases was being sold to U.S. suppliers. In response, the agency required that tissue banks test and screen donors for HIV and hepatitis B and C. The rules allowed the FDA to inspect tissue banks and to recall and destroy tissue that didn't meet the hepatitis and HIV standards.
But the industry was growing rapidly. By last year, as many as 200 organizations--some for profit, others nonprofit--were recovering, processing, and distributing tissue products to hospitals across the country. The FDA left it to the American Association of Tissue Banks, an industry group, to ensure practices that would avoid tissue contamination. The AATB set up a strict accreditation program that involves on-site inspections and a detailed review of operating procedures. The organization hired ex-FDA officials, including one former head of compliance at the FDA's Center for Biologics Evaluation and Review, to conduct inspections and application reviews. Currently, 74 tissue banks are accredited by the AATB.
But participation in the program is voluntary (and costly), and many companies opt not to join in. And the AATB cannot close down tissue banks for selling contaminated products. So, when circumstances appear dire enough, or when cases like Brian Lykins's come to light, the agency invokes its authority to prevent infectious disease. For instance, AlloSource of Centennial, Colo., fully accredited by the AATB, received a lengthy letter from the FDA on July 2 warning of numerous processing deficiencies and record-keeping problems. AlloSource has spent $1 million trying to address the FDA's concerns, a spokesperson said.
Action plan. Back in 1998, the FDA proposed new regulations that would greatly increase its authority over the tissue-bank industry. The "tissue action plan" has three key components: One requires tissue banks to register with the FDA. Another says donors must be screened for disease. The third, and perhaps the most needed, would establish "good tissue practices," akin to the high standards set for the manufacturing of pharmaceuticals. Only the first of these has been put into effect. The others are still open for public comment.
This has irked Sen. Susan Collins no end. "The FDA's action against CryoLife does not solve the underlying problem of a lack of regulation of this entire industry," says the Maine Republican. Since last December, Collins has sent two letters to the FDA urging the agency to set a deadline for putting the new rules into effect. She was told the FDA could not provide a date. "I am extremely frustrated," she says. "It is a case of bureaucratic inertia at its worst." Sen. Richard Durbin, an Illinois Democrat, wrote to the FDA in January 2001, asking the agency to outline the financial resources it would need from congressional appropriators to implement the expanded authority. He has received no response. Says Philip Noguchi, acting director of the FDA's new Office of Cellular Tissue and Gene Therapies, "We recognize that we need to finish this. It's a top priority in the next fiscal year."
This story appears in the September 16, 2002 print edition of U.S. News & World Report.