OVERVIEW OF CURRENT ALLOGRAFT TISSUE USE

Allografts are commonly used in the United States and their acceptance, availability, and safety profile have never been stronger. The numbers of grafts harvested and distributed by tissue banks in the United States have steadily increased. The American Association of Tissue Banks (AATB) recovered approximately 17,000 donor grafts in 1996, and this had increased to approximately 23,000 donor grafts in 2003.¹⁴ Over 300,000 musculoskeletal tissues were distributed in 1996, and about 1.3 million musculoskeletal grafts were distributed in 2003. It has been estimated that there have been about 4 to 5 million tissue transplants between 2000 and 2005.²⁵ Issues relating to graft procurement, sterilization, and overall tissue banking safety continue to be a concern. A recent survey by the American Orthopaedic Sports Medicine Society of over 350 members documented a concern and widespread misunderstanding of the tissue banking industry.¹⁴ Over 80% used allografts and almost 75% were concerned about safety and sterilization. Most surgeons reported not knowing much about sterilization processing and about half did not know whether their tissues were sterilized or which sterilization process was used.

Recent advancements from government agencies have made tissue banking and the use of allograft tissue safer than ever. Improved standards and techniques of tissue handling have made allografts more appealing to both surgeons and patients. Evaluation with evidence-based medicine techniques will continue to confirm the safety and efficacy of soft tissue allografts in knee surgery. The safety records of this tissue transplantation were remarkable. This chapter reviews the issues relating to the tissue banking industry, graft sterilization, and allograft safety.

CURRENT TISSUE BANK REGULATION

The U.S. Food and Drug Administration (FDA) is the government authority that regulates musculoskeletal tissue. The FDA authorizes and enforces tissue regulation to prevent the introduction, transmission, or spread of communicable diseases between states or from foreign countries into the United States. In 2004, the FDA published the “Final Rule: eligibility and determination of donors of human cells tissues and cellular and tissue-based products.”²⁰ Also published in 2004 was the Draft guidance for industry: eligibility to determination for donor of human cells, tissue and tissue-based products (HCT/Ps).²² In 2005, the FDA implemented the industry requirements for good tissue practices (GTP) for all establishments that manufacture human cell and cellular tissue–based products. The purpose of these new government regulations was to set standards for tissue banking and prevent the potential introduction, transmission, and spread of communicable diseases by allograft tissues. These standards are also in place to prevent contamination during the process of screening, procuring, and processing of allograft tissue. All tissue establishments are required to register with the FDA.

Before these recent regulations, the federal government was not able to establish or register tissue banks in the United States.

This registration and the GTP rule allow the FDA to inspect facilities anytime without notice. FDA regulations require donors to be screened and tested for human immunodeficiency virus (HIV) types 1 and 2, hepatitis B and C viruses (HBV, HCV), Treponema pallidium, and human transmissible spongiform encephalopathies.²³ In August 2007, the FDA increased screening standards by requiring recovery tissues to be negative for HIV 1 nucleic acid testing (NAT), HCV NAT, and hepatitis B core antibody (total). All tissue banks must keep a document of these tests.

The AATB, founded in 1976, is a nonprofit organization that establishes and sets voluntary standards for safe transmittal of cells and tissues.³ This organization consists of both accredited tissue banks and individual members. It promotes education and research. The goal of the AATB is to educate and prevent disease transmission with cell and tissue allografts.

The AATB first published “the standards for tissue banking” in 1984 to give recommendations and guidelines to tissue banks. These safety guidelines are periodically reviewed and updated.³ All members of the AATB must follow the published tissue bank standards for donor suitability determination (screening and testing), donor consent/authorization, tissue recovery, quality insurance/quality control, record keeping, processing, labeling, storage, distribution, and safety. The AATB has been doing on-site inspections and accreditations since 1986. Tissue banks are to be inspected every 3 years, and renewal of accreditation is granted after a formal review of any reinspection. It should be noted that membership in this trade organization is voluntary. The AATB does not have any formal disciplinary powers outside of restriction or exclusion from the organization itself. The FDA is the ultimate enforcer of tissue banks, with powers of warning letters and possibly the ultimate shutdown of the tissue banks itself.

It is currently estimated that 90% of musculoskeletal tissues are distributed through AATB-accredited tissue banks.²⁵ Through 2006 there were 95 accredited tissue banks with 70 banks involved in musculoskeletal, cardiovascular, and skin allograft tissues. The AATB requires infectious disease testing for HIV types 1 and 2 antibody, hepatitis B surface antigen, total antibody to hepatitis B core (immunoglobulin [Ig] G and IgM), human T-cell lymphotrophic virus (HTLV)–I/HTLV-II antibody, HCV antibody, NAT for HCV and HIV-1, and a syphilis assay. AATB also requires discarding allografts with cultures that are positive for clostridium or Streptococcus pyrogenes (group A streptoccoccus). Any positive final culture requires discarding of that tissue.

The American Academy of Orthopaedic Surgeons (AAOS) first released an advisory statement regarding tissue allograft use in 1991 and updated this in 2001 and 2006.¹ The AAOS urged all tissue banks to follow the AATB guidelines and standards.

The Department of Health and Human Services, through the Centers for Disease Control and Prevention (CDC), has begun to improve communication within the tissue/organ community to identify and track tissues.¹⁵ A single unique national identification number will be applied to donors and tissues that then can be tracked during the entire donation and transplantation process. This is an ongoing effort to help monitor individual tissues and ultimately improve our tissue knowledge base and increase safety standards.

In 2005, the Joint Commission (JC), which is formally known as the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), also set standards for storage of tissues intended for transplantation for hospitals and outpatient surgery centers.¹³ The JC is an independent organization separate from the FDA and is the nation’s oldest and largest accrediting body in health care. Their standards will help ensure safety at hospitals and surgery centers that handle tissues through the monitoring and recording of the use and storage of allograft tissues.

Overall, donor safety issues have been refined with the advancement of these federal laws and the increased tissue bank involvement with the AATB and its critical standards. Very few infections or tissue problems are at present occurring with tissue banks that are compliant with the AATB. With newer processing techniques, safety issues will be better monitored than ever before.

ALLOGRAFT TISSUE PROCESSING

There are two ways to transmit disease with allograft tissue. The first is by direct transmission of an infection from an infected donor. Contamination can come from the bacteria of donors, their blood, body cavity, or blood organs. The second form of contamination occurs with tissue handling during its preparation. After tissue is donated, it goes through three steps before it is packaged and delivered for implantation. The first step is donor screening, the second is tissue processing, and the third step is packaging and terminal sterilization.