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http://www.nytimes.com/2002/08/15/health/15TISS.html?ex=1030075200&en=
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August 15, 2002
Recall Is Ordered at Large Supplier of Implant Tissue
By SANDRA BLAKESLEE
The Food and Drug Administration yesterday shut down a substantial part of the CryoLife Corporation, the nation's largest processor of donated human tissue, saying the company could not adequately assure patients that its soft-tissue products were free of deadly bacteria and fungi.
The agency ordered the company to recall all soft tissues such as tendons, ligaments and cartilage processed since Oct. 3 and to withhold from the market or destroy tissue processed after that date. The tissues, obtained from cadavers, are widely used in elective orthopedic surgery to repair worn-out knees and other joints.
The agency said 27 people had developed serious infections after receiving tissue implants processed by the company, and one of them had died. The Centers for Disease Control and Prevention learned about possible problems with the tissues in November and since then has been investigating the company with the food and drug agency, which has regulatory authority over CryoLife.
The agency said it was considering a similar recall of heart valves processed by the company if they are found to pose similar contamination risks. CryoLife processes soft tissues and heart valves with identical technology, but the two types of tissue are regulated by different arms of the food and drug agency. The company plans to continue providing heart valves, veins and other products used in surgery.
The agency said people who became ill after receiving soft-tissue implants usually developed symptoms within days or a few weeks of their surgery, so people who have had implants longer than that are probably in no danger. But it can take months for infections in heart valves to produce symptoms, they said.
Recipients of CryoLife heart valves and recent recipients of soft-tissue implants should consult their doctors, the agency said.
About 650,000 Americans have surgery involving soft-tissue implants each year, and CryoLife supplies 15 to 20 percent of the market.
CryoLife is the nation's largest supplier of heart valves obtained from human donors. It processes 70 percent of the nation's heart valves and 90 percent of vascular tissue.
Recall orders like the one issued today are rare, said Dr. Mary Malarkey, director of the division of case management in the food and drug agency's Office of Compliance and Biologics Quality. The agency inspected CryoLife's operations in Kennesaw, Ga., for two weeks last March and April.
"We found significant violations from our regulations," Dr. Malarkey said. "What they were doing did not ensure tissue safety."
CryoLife responded to the agency's concerns on May 15, Dr. Malarkey said, "and we deemed their response inadequate."
The F.D.A. sent a warning letter to the company on June 17 and since then the company has not responded in "ways that assure that their material is not bacterially contaminated," Dr. Malarkey said. With the issues unresolved, the F.D.A. decided to stop the sale of soft tissues until further notice.
William Kitchens, a CryoLife lawyer, said that the company filed an appeal yesterday with the F.D.A. requesting a hearing and change in the order to allow limited distribution of tissue used for bypass surgery and dialysis patients.
With two exceptions, CryoLife has not admitted to causing any infections in any tissue recipients. According to David Fronk, vice president of clinical research, all surgery is risky and microbes can be introduced through many routes, including operating rooms and surgeons. CryoLife has never maintained that its products are absolutely safe, he said.
"You cannot sterilize tissue and maintain its functionality," Dr. Fronk said.
Most orthopedic surgery using these tissues is elective, Dr. Malarkey said, and "there are enough other processors that we hope it will not pose a supply problem."
By contrast, most heart-valve surgery is life-sustaining. It is uncertain if other suppliers could meet the demand for heart valves, which has often involved emergency surgery.
At least nine families are suing the company, accusing it of killing or maiming patients with contaminated tissues. A class-action suit on behalf of investors was filed on July 16 saying that CryoLife issued false and misleading statements regarding quality-control problems.
The New York Stock Exchange suspended trading of CryoLife stock at 12:29 p.m. when shares fell 42 percent to $5.52.
More than 150 small tissue banks across the country ? the exact number is not known ? collect tissue from human cadavers and turn it over to companies like CryoLife, which process it for transplantation. The companies charge a fee to doctors who implant the tissues. A human body can supply enough tissue for 30 orthopedic transplants.
Tissue processors use various technologies to disinfect tissues. The one used most commonly for soft tissues and heart valves involves soaking the tissues in an antimicrobial solution at a particular temperature for a certain length of time. Many such recipes are proprietary.
Companies that are members of the American Association of Tissue Banks follow nonsecret procedures, including the practice of testing tissues before they are soaked in the solution designed to kill bacteria and fungi. CryoLife is not a member of the association.
CryoLife used to test tissues before bathing them in an antimicrobial bath but stopped the practice several years ago, Dr. Fronk said, when it it decided that the step did not make tissues any safer. The company resumed the practice a couple of months ago in response to C.D.C. recommendations, he said. Apparently, the F.D.A. "does not know we are doing this," Dr. Fronk said.
CryoLife also assures tissue safety by snipping off a sliver of tissue next to the graft, and both are immersed in an antimicrobial soup. The so-called companion tissue is then ground up and thoroughly tested for contaminants, including rare forms of anaerobic bacteria and fungi.
If none are detected, the tissue graft is frozen and cleared for distribution. Once processed, tissue can remain frozen for up to 10 years.
In 1998, CryoLife was notified that two patients developed severe infections after receiving knee joints taken from the same donor, according to the C.D.C. Lawsuits were filed in those cases, and CryoLife settled them out of court.
In November, a 23-year-old Minnesota man, Brian Lykins, died shortly after receiving CryoLife tissue in routine knee surgery.
By December, the C.D.C. learned that the donor who provided Mr. Lykin's knee tissue had committed suicide in October and that the body was not refrigerated for 19 hours after being picked up by a tissue bank. That is well outside the time allowed by industry standards.
Mr. Lykins was operated on Nov. 7 and died four days later. The cause of death was a rare bacterium, Clostridium sordelli. C.D.C. investigators then found two strains of deadly Clostridia in the donor's other knee, which was still in CryoLife's warehouse. Ten other patients received grafts from the same donor and one other developed an infection. Of the 19 tissue samples not implanted, at least two had the same Clostridium sordelli bacterium that killed Mr. Lykins.
According to the C.D.C., the tissues became contaminated from bacteria in the cadaver's gastrointestinal tract that had spread through the body after death.
The agency then mounted a larger investigation of bacterial contamination of orthopedic tissue transplants. On March 15, investigators announced that of 26 infected tissues implanted into patients, half came from CryoLife. In June, the agency updated number to 54 infections, again half from CryoLife.
In March, the C.D.C. sent a list of recommendations to the company. Among other things, it said that tissues should be tested for microbes before soaking in antibacterial and antifungal solutions. Failure to test in this manner could result in the creation of superbugs ? that is bacteria and fungi that acquire resistance to antibiotics and antifungal agents.
In April, CryoLife recalled seven tissues from six states because a recipient of a company heart valves developed a Clostridium bifermentans infection ? a species common in feces, sewage and soil and associated with gas gangrene.
C.D.C. investigators have also received complaints about CryoLife heart valves, including a report that Sydney Steinberg, a 5-year-old Albuquerque girl, died from a rare fungus infection after receiving an implant. The fungus was later identified as arthrographis kalray, which is usually found in soil and rotting vegetation. Her parents are suing CryoLife, as is Ken Alesecu, now of San Luis Obispo, Calif., who developed a fungus infection after heart-valve surgery that left him, he said, using a wheelchair and suffering seizures.
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August 15, 2002
Recall Is Ordered at Large Supplier of Implant Tissue
By SANDRA BLAKESLEE
The Food and Drug Administration yesterday shut down a substantial part of the CryoLife Corporation, the nation's largest processor of donated human tissue, saying the company could not adequately assure patients that its soft-tissue products were free of deadly bacteria and fungi.
The agency ordered the company to recall all soft tissues such as tendons, ligaments and cartilage processed since Oct. 3 and to withhold from the market or destroy tissue processed after that date. The tissues, obtained from cadavers, are widely used in elective orthopedic surgery to repair worn-out knees and other joints.
The agency said 27 people had developed serious infections after receiving tissue implants processed by the company, and one of them had died. The Centers for Disease Control and Prevention learned about possible problems with the tissues in November and since then has been investigating the company with the food and drug agency, which has regulatory authority over CryoLife.
The agency said it was considering a similar recall of heart valves processed by the company if they are found to pose similar contamination risks. CryoLife processes soft tissues and heart valves with identical technology, but the two types of tissue are regulated by different arms of the food and drug agency. The company plans to continue providing heart valves, veins and other products used in surgery.
The agency said people who became ill after receiving soft-tissue implants usually developed symptoms within days or a few weeks of their surgery, so people who have had implants longer than that are probably in no danger. But it can take months for infections in heart valves to produce symptoms, they said.
Recipients of CryoLife heart valves and recent recipients of soft-tissue implants should consult their doctors, the agency said.
About 650,000 Americans have surgery involving soft-tissue implants each year, and CryoLife supplies 15 to 20 percent of the market.
CryoLife is the nation's largest supplier of heart valves obtained from human donors. It processes 70 percent of the nation's heart valves and 90 percent of vascular tissue.
Recall orders like the one issued today are rare, said Dr. Mary Malarkey, director of the division of case management in the food and drug agency's Office of Compliance and Biologics Quality. The agency inspected CryoLife's operations in Kennesaw, Ga., for two weeks last March and April.
"We found significant violations from our regulations," Dr. Malarkey said. "What they were doing did not ensure tissue safety."
CryoLife responded to the agency's concerns on May 15, Dr. Malarkey said, "and we deemed their response inadequate."
The F.D.A. sent a warning letter to the company on June 17 and since then the company has not responded in "ways that assure that their material is not bacterially contaminated," Dr. Malarkey said. With the issues unresolved, the F.D.A. decided to stop the sale of soft tissues until further notice.
William Kitchens, a CryoLife lawyer, said that the company filed an appeal yesterday with the F.D.A. requesting a hearing and change in the order to allow limited distribution of tissue used for bypass surgery and dialysis patients.
With two exceptions, CryoLife has not admitted to causing any infections in any tissue recipients. According to David Fronk, vice president of clinical research, all surgery is risky and microbes can be introduced through many routes, including operating rooms and surgeons. CryoLife has never maintained that its products are absolutely safe, he said.
"You cannot sterilize tissue and maintain its functionality," Dr. Fronk said.
Most orthopedic surgery using these tissues is elective, Dr. Malarkey said, and "there are enough other processors that we hope it will not pose a supply problem."
By contrast, most heart-valve surgery is life-sustaining. It is uncertain if other suppliers could meet the demand for heart valves, which has often involved emergency surgery.
At least nine families are suing the company, accusing it of killing or maiming patients with contaminated tissues. A class-action suit on behalf of investors was filed on July 16 saying that CryoLife issued false and misleading statements regarding quality-control problems.
The New York Stock Exchange suspended trading of CryoLife stock at 12:29 p.m. when shares fell 42 percent to $5.52.
More than 150 small tissue banks across the country ? the exact number is not known ? collect tissue from human cadavers and turn it over to companies like CryoLife, which process it for transplantation. The companies charge a fee to doctors who implant the tissues. A human body can supply enough tissue for 30 orthopedic transplants.
Tissue processors use various technologies to disinfect tissues. The one used most commonly for soft tissues and heart valves involves soaking the tissues in an antimicrobial solution at a particular temperature for a certain length of time. Many such recipes are proprietary.
Companies that are members of the American Association of Tissue Banks follow nonsecret procedures, including the practice of testing tissues before they are soaked in the solution designed to kill bacteria and fungi. CryoLife is not a member of the association.
CryoLife used to test tissues before bathing them in an antimicrobial bath but stopped the practice several years ago, Dr. Fronk said, when it it decided that the step did not make tissues any safer. The company resumed the practice a couple of months ago in response to C.D.C. recommendations, he said. Apparently, the F.D.A. "does not know we are doing this," Dr. Fronk said.
CryoLife also assures tissue safety by snipping off a sliver of tissue next to the graft, and both are immersed in an antimicrobial soup. The so-called companion tissue is then ground up and thoroughly tested for contaminants, including rare forms of anaerobic bacteria and fungi.
If none are detected, the tissue graft is frozen and cleared for distribution. Once processed, tissue can remain frozen for up to 10 years.
In 1998, CryoLife was notified that two patients developed severe infections after receiving knee joints taken from the same donor, according to the C.D.C. Lawsuits were filed in those cases, and CryoLife settled them out of court.
In November, a 23-year-old Minnesota man, Brian Lykins, died shortly after receiving CryoLife tissue in routine knee surgery.
By December, the C.D.C. learned that the donor who provided Mr. Lykin's knee tissue had committed suicide in October and that the body was not refrigerated for 19 hours after being picked up by a tissue bank. That is well outside the time allowed by industry standards.
Mr. Lykins was operated on Nov. 7 and died four days later. The cause of death was a rare bacterium, Clostridium sordelli. C.D.C. investigators then found two strains of deadly Clostridia in the donor's other knee, which was still in CryoLife's warehouse. Ten other patients received grafts from the same donor and one other developed an infection. Of the 19 tissue samples not implanted, at least two had the same Clostridium sordelli bacterium that killed Mr. Lykins.
According to the C.D.C., the tissues became contaminated from bacteria in the cadaver's gastrointestinal tract that had spread through the body after death.
The agency then mounted a larger investigation of bacterial contamination of orthopedic tissue transplants. On March 15, investigators announced that of 26 infected tissues implanted into patients, half came from CryoLife. In June, the agency updated number to 54 infections, again half from CryoLife.
In March, the C.D.C. sent a list of recommendations to the company. Among other things, it said that tissues should be tested for microbes before soaking in antibacterial and antifungal solutions. Failure to test in this manner could result in the creation of superbugs ? that is bacteria and fungi that acquire resistance to antibiotics and antifungal agents.
In April, CryoLife recalled seven tissues from six states because a recipient of a company heart valves developed a Clostridium bifermentans infection ? a species common in feces, sewage and soil and associated with gas gangrene.
C.D.C. investigators have also received complaints about CryoLife heart valves, including a report that Sydney Steinberg, a 5-year-old Albuquerque girl, died from a rare fungus infection after receiving an implant. The fungus was later identified as arthrographis kalray, which is usually found in soil and rotting vegetation. Her parents are suing CryoLife, as is Ken Alesecu, now of San Luis Obispo, Calif., who developed a fungus infection after heart-valve surgery that left him, he said, using a wheelchair and suffering seizures.
