Recipients of suspect tissue reporting adverse effects

CDC, tissue banks try to calm patients' fears

In a case described by a prosecutor as resembling a horror movie, the U.S. Food and Drug Administration (FDA) has received reports of adverse effects in patients who received human tissue grafts that were allegedly harvested from bodies in funeral homes without consent of families and, possibly, without being tested for infectious diseases as required by federal law.

The scandal surfaced late in 2005 when the FDA shut down BioMedical Tissue Services (BTS), a Fort Lee, NJ-based company that prosecutors say made $4.6 million by illegally harvesting human tissue from funeral homes and selling it for use in transplants and research. Four men, including the owner of the company, Michael Mastromarino, have been indicted by New York state prosecutors on more than 100 charges that they falsified records to conceal the source of the tissues they harvested and sold, as well as the age and health of the bodies they were taken from.

The case exposes the potential for fraud in the record keeping required for donor screening and processing. BTS is accused of falsifying details on death certificate copies kept in its files, altering information regarding testing for communicable diseases, and falsifying details about the deceased and their next of kin. The altered and inaccurate records made it impossible for the tissue processing companies that bought the tissue from BTS to accurately verify the quality and safety of the tissue.

Relevant communicable diseases for which the donor tissue is tested are HIV-1 and -2, hepatitis B virus, hepatitis C virus, and syphilis.

The FDA initially issued an advisory in late 2005 revealing preliminary findings of its investigation into BTS record keeping; the details of the case were more chilling than simple records fraud, however. Prosecutors say Mastromarino, working with an embalmer and two other associates, surreptitiously stole tissue and bone from more than 1,000 corpses. The bodies were in funeral homes. The tissue extractions allegedly took place at the funeral homes without families' knowledge or consent; afterward, removed bones were replaced with plumbing pipes before the bodies were sutured and prepared for burial.

In March 2006, the FDA updated its initial advisory to recommend, along with the Centers for Disease Control and Prevention (CDC), that health care providers offer testing to their patients who received tissue grafts originally obtained through BTS. The FDA also issued a call to patients and physicians to report any adverse effects they suspect might have resulted from that tissue.

"FDA has received reports of adverse reactions following implantation of suspect tissue," FDA public affairs spokesman Paul Richards told Medical Ethics Advisor in early May. "However, at this time, it is unclear if exposure to recalled tissue resulted in adverse reactions or infectious disease transmission. We are currently investigating reports of potential disease transmission resulting from the transplant of suspect tissue."

Industry reassures public of safety

The national association of tissue banks is reeling from the allegations and extent of the BTS charges. The American Association of Tissue Banks (AATB), a not-for-profit peer group organization founded in 1976 to facilitate the provision of transplantable cells and tissue of uniform quality in quantities sufficient to meet national needs, reacted quickly to assure the public that the processing that donor tissue undergoes makes the risk of transmission of communicable diseases — even when the tissue's origin is as clouded as that allegedly obtained by BTS — very low.

AATB publishes standards to help ensure that the tissue banking meets acceptable norms of technical and ethical performance, and provides technical information and describes procedures to foster responsible approaches to recovery, processing, preservation, and distribution of transplantable tissue.

According to AATB information, it maintains strict criteria for screening for HIV and hepatitis, selecting donors, testing and record keeping, and labeling and storage of tissues. The association inspects and accredits tissue banking organizations and certifies tissue bank personnel.

However, while some AATB-accredited tissue banks bought tissue from BTS, BTS itself was not accredited by the association.

"BioMedical Tissue Services is not now, nor has it ever been, accredited by the AATB," association CEO P. Robert Rigney, Jr., JD, said in a statement released at the time charges were announced against the BTS principals. "In fact, BTS has never applied for AATB accreditation."

According to federal law, tissue for potential donations is removed by registered tissue recovery agencies, of which BTS was one. Tissue recovery agencies are subject to FDA regulations, the "Current Good Tissue Practices" rule. During an inspection of BTS late in 2005, the FDA uncovered deviations in record keeping that raised red flags about the safety of the tissue harvested by the company.

Rigney outlined the processing that donor tissue undergoes before being banked, emphasizing that the processing is conducted according to FDA regulations and AATB standards, resulting in "multiple layers of screening, testing, quality assurance, and quality control measures." When tissue is harvested and processed according to industry standards, the following sequence of steps occurs:

  • Following recovery, tissue is quarantined until a donor suitability determination is made. The donor is tested for communicable diseases (HIV-1 and -2, hepatitis B, hepatitis C, human T-cell lymphotropic virus-I and -II, and syphilis), in some instances using multiple tests and methodologies; the FDA has said that because blood samples and records accompanying the donor tissue from BTS are suspect, it cannot be determined if the BTS tissue met this criteria;
  • A medical doctor reviews available medical records and donor medical and social histories, and makes the final determination on the donor's suitability;
  • Once the donor is accepted, the tissue is processed in controlled environments to prevent contamination and cross-contamination. Processing methods are validated, as required by the FDA and AATB. Rigney says most musculoskeletal tissues are highly processed, cleaned, treated with antibacterial and virucidal agents, and subjected to gamma irradiation or another method of viral inactivation or sterilization.

"To the best of our knowledge and belief, this is the first time in the 29-year history of the AATB where allegations have been made of possible widespread falsification of donor consent forms and medical records," said Rigney.

CDC recommends testing

The CDC has posted information and advisories about the safety of donor tissues on its web site (www.cdc.gov/ncidod/dhqp/tissuetransplantsFAQ.html) and advises physicians about testing their patients should receive if they were recipients of donor tissue:

  • Patients who received tissue implanted more than six months ago should be given the following tests: HIV antibody, antibody to hepatitis B core antigen, antibody to hepatitis C virus, non-treponemal syphilis test (e.g., RPR or VDRL), and treponemal syphilis test (TP-PA or ELISA). If all tests are negative, the patient is unlikely to contract any of the diseases from donor tissue, and follow-up testing is not necessary, the CDC advises;
  • Patients who received donor tissue less than six months ago can be offered the same tests described above, but should be re-tested six months after the tissue was implanted.

Nucleic acid tests, such as PCR assays, should not be used in place of the antibody tests recommended, the CDC advises.

Adverse reactions should be reported to the bank from which the tissues were obtained, or to the FDA's MedWatch voluntary reporting program, or both, the CDC, FDA, and AATB recommend. MedWatch is accessible at www.fda.gov/Medwatch/report.htm, or by calling (800) FDA-1088.

Following the advisory issued by the FDA, all BTS tissue remaining in banks was quarantined, and any that had been distributed for transplant was recalled.

As of late April, dozens of class-action lawsuits involving hundreds of tissue recipients had been filed in state and federal courts; that number could grow exponentially as the number of individual grafts distributed numbered in the thousands, according to investigators.

[For more information:

U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Rockville, MD. Phone: (301) 827-2000.

American Association of Tissue Banks, 1320 Old Chain Bridge Rd., Suite 450, McLean, VA 22101. Phone: (703) 827-9582. Web site: www.aatb.org.]