Medical Standards for Eye Banking

Eye Bank Association of America Medical Standards

The EBAA’s Medical Standards define the minimum standards of practice for eye banking functions and assure “acceptable levels of quality, proficiency, and ethics in dealing with ocular tissue for transplantation.” These standards are determined by its Medical Advisory Board, a committee composed of corneal surgeons, eye bankers, and research scientists, with input from an FDA representative. The medical standards are based on science specific to ocular tissue when it is available and consensus following informed discussion when it is not. The standards are revised twice a year, reviewed and approved by the American Academy of Ophthalmology (AAO), and distributed to EBAA member banks. The EBAA Medical Standards is a living, constantly evolving document, which reflects a delicate balance between science and practice, placing patient safety as a top priority.

The EBAA Medical Standards are more comprehensive than current federal or state regulations, as they cover all aspects of eye banking including recovery and preservation of ocular tissue: evaluation of tissue for surgical use, including slit lamp examination and specular microscopy; tissue processing for lamellar or other specific surgical applications; distribution, packing, and shipping of tissue for ocular surgery or other uses; and maintenance of donor and recipient case records. Contraindications for transplant include diseases and conditions that pose a risk to the success of ocular surgery. The FDA donor eligibility regulations have been moved to appendices to make the standards applicable internationally.

Oversight of eye banking policies and operations by a qualified, corneal fellowship-trained medical director is required. The EBAA requires eye banks to request postoperative outcome information from the transplanting surgeon. Reporting of adverse reactions, defined as primary graft failure and early regraft, endophthalmitis, keratitis, corneal dystrophy or degeneration, malignancy, and transmission of systemic disease, has been required since 1990. The EBAA maintains a registry of reported adverse reactions as a means of detecting trends and identifying potential risks. Promulgation of the EBAA Medical Standards is believed to be a major factor in the remarkably low frequency of adverse reactions associated with ocular tissue transplantation.

Adherence to the medical standards is assured via EBAA’s on-site inspection and accreditation process, which occurs at least every 3 years. Volunteer inspection teams comprising a corneal surgeon and a certified eye bank technician conduct regular, announced site inspections to assess compliance with the medical standards. The inspection includes a comprehensive review of the banks’ standard operating procedures, donor files, technician training and education, equipment maintenance, technician proficiency, and quality assurance procedures. The findings are presented, and eye banks have an opportunity to make corrective actions within specified time limits to address areas of noncompliance. Unannounced inspections may occur when there is evidence of noncompliance with the medical standards that is potentially threatening to eye bank staff or recipient safety. The inspection teams form the EBAA Accreditation Board, which meets semiannually to discuss the results of the site visits and to determine accreditation status. While EBAA membership and accreditation are voluntary, the vast majority of eye banks in North America are EBAA members, and most corneal transplant surgeons use tissue from accredited banks.

Federal and State Regulations

Initially, federal and state regulation of eye, tissue, and organ banks centered on issues of consent, payment, and promotion of donation to ensure an ample supply of organs and tissues. More recent regulations have focused on tissue safety, particularly disease transmission.

The Uniform Anatomical Gift Act (UAGA) of 1968 stated that a signed and witnessed donor card was sufficient legal permission for organ or tissue removal after death. Versions of this law were passed in all 50 states by 1970, substantially simplifying the paperwork necessary to donate body parts for therapeutic, teaching, or research purposes. The UAGA was updated in 1987 and again in 2006 to reflect changes in federal law and regulations as well as changes in donation practices.

Several states have enacted legislative consent laws that allow tissue to be recovered with the approval of the medical examiner or coroner with “no known objection” from the legal next of kin. The first of these presumed consent legislations was passed in Maryland in 1975, resulting in a significant increase in availability of donor corneas. While presumed consent laws remain controversial in some areas of the United States, many European countries and Singapore have moved toward an opt-out system. The United States operates under a model of first-person consent with the decision of the deceased made known through an advance directive, donor card, driver’s license, or donor registry or the direct permission of the next of kin. Most states have passed first-person consent laws and established donor registries. Currently, 56% of corneas are recovered annually from registered donors in the United States.

The most important legislation to increase organ and tissue donation is the Condition of Participation (CoP) for Organ, Tissue, and Eye Procurement for hospitals participating in the Medicare and Medicaid Programs. The CoPs require hospitals to have an agreement with their federally designated organ procurement organization (OPO), with at least one eye bank and tissue bank to recover organs and tissues; require hospitals to report all deaths to the OPO in a timely manner; and specify the approach to families in offering the option of tissue and organ donation. Disagreement may arise when next of kin refuses consent, despite the presence of a signed donor card. Most recovery agencies defer to the family’s wishes in order to avoid controversy and potential legal entanglements. Failure to recover tissue in these cases is not in concert with the wishes of the deceased, although it is unlikely to result in civil or criminal penalties.

The sale or purchase of human tissue was specifically outlawed in 1984 with passage of the National Organ Transplant Act. The Act made it “unlawful for any person to knowingly acquire, receive, or otherwise transfer any human organ for valuable consideration for use in human transplantation.” Corneas and eyes were included in the definition of human organ. The term “valuable consideration” was defined to allow reasonable payments for costs associated with recovery, processing, evaluation, and distribution of tissue. A number of bills proposing various means of compensation for both living and cadaveric donors have been introduced in Congress with the intention of increasing solid organ donations, but none has received serious consideration. The Barcelona Principles, a global ethical agreement on the use of donated human tissue for ocular transplantation, research, and future technologies, include a clear statement to protect and maintain “altruistic and voluntary donations” as a public resource for the shared benefit of all. It is available online at the Global Alliance of Eye Bank Associations website ( http://www.gaeba.org/wp-content/uploads/2018/05/GAEBA-2018-The-Barcelona-Principles-FINAL.pdf ).

The authority for federal regulation of eye banking is based on Section 361 of the Public Health Service Act of 1944, which authorizes regulations “necessary to prevent the introduction, transmission, or spread of communicable diseases.” The FDA began a process to regulate eye banking practices formally in the United States in the 1990s, following reports of human immunodeficiency virus (HIV) transmission from tissue transplantation, especially bone. A final rule that spelled out requirements for donor history and physical examination; mandated serologic testing for HIV type I and II, hepatitis B, and hepatitis C; and defined regulations pertaining to recalls, inspections, and record retention was adopted as part of the Code of Federal Regulations in 1997. Additional regulations were issued requiring establishment registration and listing, donor suitability requirements, good tissue practice rules, and inspection and enforcement.

The Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-based Products was added in 2004, which expanded the requirements for screening and testing donors for risk factors for, and clinical evidence of, relevant communicable disease agents or diseases (RCDADs). The November 2004 Current Good Tissue Practice (CGTP) Final Rule requires that tissues be handled according to procedures designed to prevent contamination and to preserve tissue function and integrity. The rule outlines required practices such as proper tissue handling, storage, processing, labeling, and recordkeeping procedures and requires establishment of a quality program to ensure compliance with these regulations. Most of these issues are currently addressed by EBAA Medical Standards.

In addition, the FDA has issued numerous “Guidance for Industry” documents dealing with specific aspects of donor screening and testing for relevant communicable diseases that pose a risk of transmission, the types of test kits that can be used for serologic testing of cadaveric blood, further clarifications of the CGTP requirements, definitions of minimal tissue manipulation, and adverse reaction reporting requirements. Blood tests currently required by the FDA for screening eye donors are listed in Table 25.1 . Additional “Guidance for Industry” recommendations are issued in draft form as needed and finalized after a comment period. Guidance documents can be accessed online at the fda.gov website ( https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/tissue-guidances ). Although guidance documents are considered nonbinding recommendations, once in final form, eye banks must be able to justify any deviations from the recommended practices or face enforcement action from the FDA.

The FDA inspectors conduct unannounced site visits. Areas of noncompliance may lead to issuance of an FDA Form 483 and must be addressed within specified time limits. Continued noncompliance can lead to legal action by the FDA. Inspectors’ findings are a matter of public record, as are records of tissue recalls. A recall may be ordered by the FDA, or initiated voluntarily by an eye bank, if violations of the Code of Federal Regulations are discovered, which indicate a potential risk for transmission of a relevant communicable disease. A recall requires notification of the transplanting surgeon of the receipt of positive screening results after release of tissue, but it does not require removal of transplanted tissue. Recalls and related market withdrawals are discussed in greater detail in the following section.

Many states require eye banks to obtain a permit, license, or registration in order to provide human tissues in those states. New York, Florida, and California have comprehensive regulation of tissue banks and license and inspect facilities that recover, process, store, or distribute human tissue. In addition, New York and Florida require banks to report adverse incidents to public health authorities. While an exhaustive review is beyond the scope of this chapter, one notable example is New York’s requirement for the performance of donor rim cultures.

Standards Relating to Safety of Tissue

Medical standards relating to the safety and efficacy of tissue are primarily concerned with reducing the risk of disease transmission and ensuring that the transplanted tissue is of adequate optical and mechanical integrity for its intended use. The EBAA adverse reaction registry has been tracking reported cases of disease transmission and primary graft failure since 1991 ( Table 25.2 ). Ophthalmic disorders that can be conveyed via corneal transplantation include corneal dystrophies and degenerations, microbial keratitis, and endophthalmitis. Systemic viral infections, prion disease, and malignancies also have the potential for transmission via corneal grafting. To counteract the inherent tendency toward underreporting in voluntary registries, the definition of a reportable adverse reaction has changed over time to include events that are possibly related to tissue in addition to those that are probably related to tissue. In the case of systemic diseases such as hepatitis, human immunodeficiency virus, syphilis, West Nile virus, and prion disease, any occurrence in a recipient is reportable whether it is suspected to be related to donor tissue or not.