FDA says patient death led to action
The Food and Drug Administration (FDA) has ordered Cryolife Inc. of Kennesaw, GA, a human tissue-processing firm, to recall distributed human tissue processed since Oct. 3, 2001. Under the order, the firm must also withhold from the market or destroy tissue processed after that date. The action was taken because the company could not ensure that the human tissue it processes for transplantation is free from fungal and bacterial contaminants, the FDA announced.
Tissue from a donor processed by Cryolife on and after Oct. 3, 2001, has been associated with the Nov. 7, 2001, death of a patient who received a soft tissue implant during reconstructive knee surgery. U.S. tissue banks distribute about 750,000 allografts annually for transplantation. Currently, some tissue banks report using aseptic methods for processing musculoskeletal tissue allografts, and some use post-processing cultures as quality-control indicators.
However, the end product may not be sterile, as underscored by several recently reported cases — including the aforementioned one — of allograft-associated infectious complications.1 (See Hospital Infection Control May 2002 under archives at www.HIConline.com.)
During an inspection of CryoLife from March 25 through April 12, 2002, the agency found numerous, significant violations of its regulations. The FDA issued a warning letter to Cryolife on June 17, 2002, after determining, among other things, that the firm had neither adequately investigated its validation of processing and testing methods, nor implemented recommendations from the Centers for Disease Control and Prevention.
Current federal regulations for human tissue require firms to prepare, validate, and follow written procedures to prevent infectious disease contamination or cross-contamination during tissue processing. Contamination may be caused by a variety of infectious disease agents including viruses, bacteria, fungi, and transmissible spongiform encephalopathy (TSE)-associated prions.
The FDA’s concerns described in the order relate specifically to bacterial and fungal contamination of soft tissues such as cartilage and tendons. The FDA’s investigation revealed, among other things, that of those standard operating procedures implemented by Cryolife to prevent infectious disease contamination or cross-contamination, many were not followed. In addition, Cryolife improperly distributed tissue from a donor after the firm confirmed the presence of harmful microorganisms in tissue samples from the same donor, the FDA charged.
If a bacterial or fungal infection were to occur following a tissue transplant, the signs and symptoms would usually appear within days to weeks after transplantation. Therefore, it is unlikely that patients who have not received a transplant recently are likely to be at future risk. However, concerned patients are encouraged to contact their physicians, the FDA stated.
A message posted on the CryoLife Inc. web site said the company has tightened its criteria for discarding donor tissue suspected of being contaminated. CryoLife hired an outside consultant to advise the company on scientific and technical issues, the company stated.
The firm has contracted with an independent microbiological laboratory to assist in validation testing and has initiated additional in-house studies to improve its processes and test monitoring. CryoLife and the FDA have agreed to meet and discuss further issues, the company reported.
1. Kainer M, Castor M, Ledell K, et al. Clostridium sordellii infection associated with cartilage allograft transplantation: The need for tissue safety. Abstract 95. Presented at the annual conference for the Society for Health Care Epidemiology of America. Salt Lake City; April 6-9, 2002.