On September 29, 2005, a human tissue-processing company discovered inaccuracies in donor records forwarded from a tissue-recovery firm and notified the Food and Drug Administration (FDA). An FDA investigation determined that the recovery firm, Biomedical Tissue Services, Ltd. (BTS) (Fort Lee, New Jersey), recovered tissues from human donors who might not have met donor eligibility requirements and who were not screened properly for certain infectious diseases. In October 2005, BTS and the five processors* that had received the tissues, working with FDA, issued a recall for all tissues recovered by BTS. The continuing FDA investigation determined that information for some donors (e.g., cause, place, or time of death) was not consistent with death certificate data obtained from the states where the deaths occurred. The investigation also determined that BTS had failed to recover tissues in a manner that would prevent contamination or cross-contamination and failed to control environmental conditions adequately during tissue recovery. These failures were violations of the Current Good Tissue Practice Rules† (effective May 25, 2005), which require manufacturers to recover, process, store, label, package, and distribute human cells, tissue, and cellular and tissue-based products (HCT/Ps) to prevent introduction, transmission, or spread of communicable diseases. In January 2006, FDA ordered BTS to cease manufacturing and to retain all HCT/Ps.
The tissues recovered by BTS had been sent to five processors, who distributed them through one or more sub-distributors or directly to clinicians and health-care facilities. CDC learned that, during June 2002–October 2005, approximately 25,000 BTS-recovered tissue products were distributed to all 50 states and internationally. Most of these tissue allografts were bone or demineralized bone matrix; others included skin and soft tissue (e.g., tendons or fascia lata). Before distribution, tissues were disinfected by tissue processors to reduce or eliminate contamination with bacteria, fungi, or viruses.
During September-October 2005, the five tissue processors recalled all products that had been produced from BTS tissues. Each of the processors and related distributors issued letters to consignees (i.e., health-care facilities or clinicians) to notify them of the recall and request return of unused products. The letters included a recommendation by FDA and CDC that transplant recipients be notified of the recall and offered access to testing for the communicable diseases for which donor screening is required: human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis.
In March 2006, FDA determined that, in some instances, blood samples submitted for disease screening had not come from the persons from whom the linked tissues had been obtained. This finding cast doubt on the blood sample–screening status of the tissue donors, and FDA and CDC issued an update‡ that strongly recommended health-care providers offer patients access to or referral for testing for HIV, HBV, HCV, and syphilis. CDC recommendations§ for testing persons who received BTS tissues call for patients whose tissue implants have been in place >6 months to be offered the following tests: HIV antibody, antibody to hepatitis B core antigen, antibody to hepatitis C virus, a non-treponemal syphilis test (i.e., rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]), and a treponemal syphilis test (i.e., Treponema pallidum particle agglutination [TP-PA] or any enzyme-linked immunosorbent assay [ELISA] test). Patients whose tissue implants have been in place <6 months can be offered the same tests; however, they also should be retested 6 months after the tissue was implanted. If all of these tests yield negative results, the likelihood that one of the diseases was contracted from an implanted BTS tissue is small; no further follow-up testing is recommended. Patients who have a positive result for any of these tests should undergo confirmatory or supplemental testing. Positive test results in recipients of BTS tissue should be reported to local or state health departments, the tissue distributor, FDA's MedWatch program (http://www.fda.gov/medwatch), or CDC at telephone 800-893-0485.
FDA and CDC are continuing to investigate reports of BTS tissue recipients who have undergone screening and tested positive for one of the four tested diseases. Some positive results would be expected in any U.S. population tested; the prevalence of current or past infection with HIV, HCV, and HBV is approximately 0.5%,2 1.8%,3 and 4.9%,4 respectively. Transmission of infection via tissue allografts is rare, but transmission of HIV5 and HCV6 to tissue recipients has been documented previously. However, the relationship between implanted BTS tissue and positive test results reported to FDA and CDC is difficult to ascertain because of inaccurate BTS donor records and, in some cases, the absence of properly linked donor blood samples.
Allograft recipients who are concerned that they might have received tissue recovered by BTS should contact the health-care providers who performed their implants. Clinicians with specific questions about the recovery history of tissues they have used in implants should contact the health-care facility or the distributor that provided the tissues. State or local health departments can determine (1) where BTS-recovered tissues were sent and (2) whether they were implanted by contacting the tissue processors and working with local hospitals and health-care facilities. Tissue processors and distributors maintain information they receive regarding tissue providers and health-care facilities in each state that received products associated with recalls. However, because information regarding the tissue recipient might not be available to tissue processors and distributors, state or local health departments might need to provide patient follow-up by contacting the health-care facilities where implantation occurred.
M Malarkey, R Solomon, MD, C Witten, MD, PhD, E Bloom, PhD, M Wells, MPH, M Braun, MD, R Wise, MD, C Zinderman, MD, Center for Biologics Evaluation and Research, Food and Drug Administration. DB Jernigan, MD, MJ Kuehnert, MD, A Srinivasan, MD, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases (proposed); S Wang, MD, EIS Officer, CDC.
REFERENCES: 6 references available.
*Regeneration Technologies, Inc. (Alachua, Florida); LifeCell Corporation (Branchburg, New Jersey); Tutogen Medical, Inc. (Alachua, Florida); Central Texas Regional Blood and Tissue Center (Austin, Texas); and Lost Mountain Tissue Bank, Inc. (Kennesaw, Georgia).
†Available at http://www.fda.gov/bbs/topics/news/2004/new01137.html.
‡Available at http://www.fda.gov/cber/safety/bts030206.htm.
§Available at http://www.cdc.gov/ncidod/dhqp/tissuetransplantsfaq.html.
Brief Report: Investigation into Recalled Human Tissue for Transplantation—United States, 2005-2006. JAMA. 2006;296(11):1347-1348. doi:10.1001/jama.296.11.1347