Fifty-Ninth ACBTSA Meeting September 4 - 5, 2024 - Meeting Summary

Executive Summary

The Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA) convened its 59th meeting, which occurred over two days. On the first day, speakers described the history and current landscape of tissue transplantation in presentations entitled (1) “U.S. Centers for Disease Control and Prevention (CDC) Tissue and Safety Investigations: Lessons Learned and Opportunities for Improvements”; (2) “Regulatory Oversight of Tissue Establishments and Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”; (3) “Tissue Product Tracing During a Tissue-Derived Tuberculosis Outbreak”; (4) “Regulations on Blood Traceability: Lookback and Adverse Reaction Reporting”; (5) “Solid Organ Transplant Lookback, Traceability, and Disease Transmission Reporting Requirements”; (6) “Centers for Medicare and Medicaid Services (CMS) Regulatory Oversight Over Healthcare Facilities, Infection Control Requirements: Opportunities for Enhancing Tissue Safety”; and (7) “How do Tissue Establishments Conduct Product Tracking?”. The second day included discussion and voting on recommendations proposed by the Tissue Biovigilance Subcommittees. Eleven recommendations were passed by the ACBTSA.

Meeting Summary

Day One Welcome and Opening Remarks

ADM Rachel Levine, MD, Assistant Secretary for Health, provided brief welcoming remarks and described the importance of the ACBTSA and tissue transplant operations to patients across the nation. Kaye Hayes, MPA, Deputy Assistant Secretary for Infectious Disease and Director of the Office of Infectious Disease and HIV/AIDS Policy (OIDP), led the swearing in of seven new members joining the ACBTSA and acknowledged the service of ACBTSA members whose service had recently concluded. James Berger, MS, MT (ASCP), SBB, conducted roll call to confirm a quorum.

Diane Wilson, MSN/MHA, Chief Operating Officer of Solvita welcomed ACBTSA members to the public meeting and provided an overview of the agenda. She noted that the first day of the meeting would include presentations of perspectives on tissue transmitted infections, traceability challenges, and regulatory overside. The second day of the meeting would consist of discussion and voting on recommendations proposed by the Tissue Biovigilance Subcommittee, which was formed in 2022 in response to transplant derived infections of Mycobacterium tuberculosis and Mycoplasma hominis.

Michael Bell, MD, Acting Director of the CDC Division of Healthcare Quality Promotion, notes that transplantation systems in the United States are faced with gaps including the traceability of tissues from donors to recipients by end-users, lack of common nomenclature, coding and labeling procedures, and lack of requirements to monitor or report adverse events by consignees and end-users. These gaps result in increased risks of patient harm, particularly when using products which cannot be completely sterilized. These challenges, alongside the increased importance of tissue transplantation, highlight the importance of the ACBTSA in proposing recommendations to improve and support national transplantation systems.

CDC Tissue Safety Investigations: Lessons Learned and Opportunities for Improvements

Sridhar Basavaraju, MD, FACEP, Director of the Office of Blood, Organ, and Other Tissue Safety (BOOTS), Centers for Disease Control and Prevention (CDC)

Dr. Sridhar Basavaraju described the history of transplant- and transfusion-derived infections that have been investigated by the CDC, and the lessons learned from these infectious outbreaks that can be used to inform the later discussion of recommendations proposed by the Tissue Biovigilance Subcommittee.

The CDC has investigated numerous donor-derived infections, beginning with cases of donor-derived rabies and human immunodeficiency virus (HIV) in 1979 and continuing through to the present day. These cases highlighted that current tissue tracking and traceability systems are insufficient for monitoring products obtained from a donor to consignees or end-users. Health care systems often do not have common nomenclature, coding, or labeling; may not require consignees or end-users to monitor or report adverse events; do not effectively monitor tissue usage; do not have adequate systems in place to detect or diagnose potential donor-derived infection events; and are not able to provide reliable metrics regarding tissues collected or implanted.

Additional efforts by a working group, which convened in 2005 and consisted of representatives from the CDC, the U.S. Food and Drug Administration (FDA), and the Health Resources and Services Administration (HRSA), identified several measures to improve the safety of tissue transplantation. These included: the implementation of a unique donor ID system able to trace tissues from a donor to an end-user; development of a system capable of tracing products from a donor to a recipient and from a recipient to the donor; a system able to confer notifications of donor-derived infections; increasing the frequency of reporting adverse events by health care facilities; and the development of educational or guidance materials for disbursal among clinicians, professionals, and patients.

A gap assessment of tissue biovigilance commissioned by the Health and Human Services Office of the Assistant Secretary for Health (HHS OASH) in 2009 continued to identify challenges related to tissue tracking and traceability. The gap assessment concluded with several recommendations: (1) providing additional support for national biovigilance programs including donor-derived materials, (2) developing a cross-organizational platform for reporting adverse events, and (3) enhancing mechanisms for the surveillance, investigation, and reporting of transplantations.

Recommendations designed to combat tissue tracking and traceability challenges were proposed to the ACBTSA in 2015. Recommendations included establishing a common identification system for all human tissue products, creating a database of all organ and tissue donation events, creating oversight mechanisms for use in health care settings to support both traceability and tissue surveillance, supporting educational efforts for health care providers to improve informed consent procedures, and offering incentives for compliance with these recommendations. However, these recommendations were not nationally implemented.

Two notable programs were developed to address challenges associated with tracking, traceability, and reporting adverse events. A pilot of the Transplantation Transmission Sentinel Network was implemented by nine tissue organizations in 2008 and recorded almost 1,900 donation events and 900 tissue implant events. During the pilot period, the project faced challenges resulting from multiple donor IDs being applied to donor-derived products as they were transferred between organizations, lack of a common adverse event recognition system, lack of a notification system, and lack of reporting requirements by participants, leading to the end of the network.

An additional attempt to improve tissue tracking and traceability was implemented by the FDA in the form of implant cards. These cards are provided by tissue distributors alongside tissue products and were intended to be completed by the end-users and returned to tissue product manufacturers. Following a donor-derived outbreak of Mycoplasma in 2015, several end-users failed to return implant cards to the manufacturing facilities; many implant cards were missing information or contained incorrect information. Overall, 7 out of 30 tissue products had incorrectly completed or incorrectly submitted implant cards, increasing the difficulty of determining the final disposition of these products.

Difficulties in determining the final disposition of tissue products continues to be a recurring challenge. A case of donor-derived tuberculosis infections in 2021 identified that approximately 4 percent of all products could not be traced to their final disposition.

Beyond traceability, the recurrence of donor-derived tuberculosis infections that occurred in 2021 and 2023 indicates a need to increase the required incubation time for identifying contamination with tuberculosis. Investigation of these outbreaks revealed that donor-derived materials can be positively cultured for tuberculosis following a 40-day incubation period.

Dr. Basavaraju stresses that the same issues continue to recur. Challenges associated with tissue tracking and traceability are pervasive and continue to impact patient safety. The challenges of tissue tracking and safety are increasing as tissue transplantation becomes more prevalent. The American Association of Tissue Banks (AATB) reports that there are over 58,000 tissue donors annually, and up to 2.5 million implanted tissues. These reflect national estimates; however, the quantity of donors and implanted tissues may be even greater as current tracking is insufficient to provide a reliable estimate. It is important to respond to challenges of traceability, data collection and the recognition and reporting of adverse events. The CDC is seeking to engage in tissue-safety focused efforts including surveys, conversations, and partner engagement. 

Discussion

Dr. Cassandra Josephson remarked upon two issues surrounding the importance of tissue biovigilance. She described a tissue donation event that occurred in the late 2000’s involving the potential contamination of donor-derived materials, falsification of donor information, and struggle to identify people who may have been exposed to infectious materials. Further, she expressed concern that children, who are also recipients of donor-derived materials, may receive potentially infectious materials.

Dr. Raymond Goodrich affirmed that issues related to tissue tracking and safety are recurrent. Given that attempts made to combat these issues have been unsuccessful, he questioned what will make new attempts successful. Dr. Basavaraju responded that the recommendations proposed by the Tissue Biovigilance Subcommittee have been developed to be realistic and actionable.

Michelle Kim asked about consequences or penalties following reporting of incorrect donor information or poor donor vetting. Dr. Basavaraju indicated that the CDC is not typically involved in any subsequent actions, but that health care organizations and tissue manufacturers are often sued. Scott Brubaker will discuss the implications of these investigations in his talk.

Dr. Jed Gorlin requested further insight regarding the potential for transmission events to occur following negative bacterial culture tests. Dr. Basavaraju clarified that tests can be impacted by products having few colonies and the presence of native inhibitors in tissue products. Therefore, bacteria or viruses may be present within a tissue sample but below the limit of detection.

Dr. Susan Galel explained that choosing infections to be tested for in donor-derived materials is difficult because (1) limited materials are available for testing, (2) there is a wide variety of potential infectious agents, (3) validated tests in relation to different donor-derived tissues are limited, and (4) there are several stages between identifying a donor and implanting materials. Lou Barnes indicated that tests are often mandated by accrediting organizations, but that some infections (e.g., tuberculosis) have fewer applicable tests. Dr. Claudia Cohn added that there is always the risk that some diseases will not be observed upon testing and that donor review and product traceability are important for identifying potential issues beforehand and retroactively responding to infection potential.

Dr. Josephson stressed the importance of patient consent procedures. Patient consent procedures, particularly in regard to dental procedures, may be insufficient to inform the patient of risks associated with receiving donor-derived materials.

Dr. Timothy Pruett noted that donor histories are often reliant on information obtained from a proxy. He questioned the reliability of proxies and whether there are requirements for who can serve as a proxy. Dr. Basavaraju responded that information relayed by any individual has the potential to be inaccurate; obtaining patient information from the potential donor or a proxy is highly likely to be inaccurate in some regards.

Dr. Daniela Hermelin asked whether it would be possible to obtain information and proactively identify potential donors.

Dr. Elisa Gordon commented that clinicians seeking to gain informed consent from patients should pay special attention to the CDC’s transplant tissue risk categorization during the informed consent process for potential transplant recipients.

Regulatory Oversight of Tissue Establishments and HCT/Ps

Scott Brubaker, Senior Advisor of the Office of Cellular Therapy and Human Tissue, Office of Therapeutic Products Center for Biologics Evaluation (CBER), U.S. Food and Drug Administration (FDA)

The Code of Federal Regulations (CFR) title 21 part 1271, also known as the Current Good Tissue Practice (CGTP), describes requirements and regulations related to tissue biovigilance. These include information for the registration of manufacturing facilities, donor eligibility, processing, and reporting related to human cells, tissues, and cellular and tissue-based products (HCT/Ps). HCT/Ps include human-derived materials such as bone, ligaments, skin, gestational or reproductive materials, and corneas. Materials such as vascularized organs, whole blood, and materials obtained from non-human sources are not considered to be HCT/Ps and are not included within the 21 CFR part 1271 regulations. Manufacturing facilities registered with the FDA are required to identify all HCT/Ps that will be produced by the facility, their donor type, and manufacturing and preservation processes that will be performed.

Six criteria would allow HCT/Ps to be exempt from the regulations presented within 21 CFR part 1271. Two exemptions are pertinent when discussing end-users of tissue products. The first is when HCT/Ps are intended for autologous re-implantation (i.e., materials harvested from an individual and intended to be re-implanted within the same individual). The second pertinent exemption is for establishments that do not recover, screen, test, process, label, package, or distribute HCT/Ps, but only receive or store HCTP/s for use within the facility.

The FDA has developed for non-exempt HCT/Ps based on the risks associated with their use. HCT/Ps that receive minimal manipulation are regulated under section 361 of the Public Health Service Act. These HCT/Ps are intended for homologous use, do not involve the combination of cells or tissues with other materials (not including preservation or sterilization agents), and either do not have a systemic effect and function independently of living cells or have a systemic effect and are dependent on the function of living cells. Products that do not meet these criteria are regulated under both section 351 and section 361 of the Public Health Service Act. The following regulations pertain to facilities which handle non-exempt HCT/Ps as described under 21 CFR part 1271. These regulations include methods for determining donor eligibility, record keeping and product labeling, and tracking.

Regulations pertaining to donor eligibility include descriptions of screening donors for transmissible infections (e.g., HIV, Hepatis B, and Hepatitis C) and communicable disease agents (e.g., sepsis and West Nile Virus). Requirements for screening transmissible infections and communicable disease agents may change depending on their prevalence within the donor population or the tissues being acquired (e.g., donors no longer need to be screened for Zika virus, but donor reproductive tissues must be tested for Chlamydia trachomatis). Further, the regulations specify the types of tests required during donor screening (e.g., antigen tests and nucleic acid tests) and provides guidance for reducing the transmission risk of certain infectious or communicable disease agents (e.g., Mycobacterium tuberculosis and agents associated with sepsis).

Regulations pertaining to record maintenance and product labeling include labeling product containers with distinct identification codes (e.g., alphanumeric codes) that can be used to link HCT/Ps to the donor and all relevant records (e.g., donor eligibility, manufacturing techniques, and methods of preservation).

FDA guidance documentation describes requirements for tracking HCT/Ps. Generally, facilities performing any manufacturing of HCT/Ps are required to ensure that they are able to assist the investigation of any transmission events and are able to engage in corrective actions. Assisting investigations includes establishing and maintaining HCT/P tracking systems capable of tracing donor materials to their final disposition and the disposition of materials back to the original donor. To be compliant with regulations for record maintenance and product labeling, tissue facilities must ensure that all products are labeled with distinct identification codes. Further, consignees must be informed of these requirements and tracking systems being applied upon receipt of materials.

HCT/P deviations represent any action that is not in alignment with regulations, such as unexpected or unforeseeable events that may relate to the potential transmission of communicable diseases or contamination of HCT/Ps. All deviations must be reported to the FDA within 45 days of discovery. Deviations not reported to the FDA that are discovered during inspection of a facility result in a citation. Facilities that receive multiple citations may receive a warning letter.

Facilities are also required to report adverse events as part of the regulations pertaining to quality program functions. Adverse events must be reported if they may have resulted from an HCT/P and are (1) fatal, (2) life-threatening, (3) result in impaired function, (4) result in permanent damage, or (5) require medical intervention. Facilities must report these events to the FDA within 15 days and facilities must provide to the FDA within 15 days of the initial report additional follow-ups describing investigative measures.

Following the report of an adverse event, Center for Biologics Evaluation and Research (CBER) initiates a coordinated approach to review all information received and conduct follow-up reports. Information such as culture reports, patient symptoms or outcomes, and product codes is routinely requested to assist the investigation. Sharing these types of patient information is permitted under the Health Insurance Portability and Accountability Act (HIPAA). Facilities are further required to engage in the appropriate follow-up of adverse events (e.g., notifying entities that have engaged with the affected HCT/Ps, quarantine and recall products).

In 2023, 229 deviations were reported to the FDA. Of those, 181 resulted in MedWatch reports. Manufacturers were the primary reporting organization, with few reports having been submitted by end-users. Infectious reports were most likely to be submitted for bone, skin, and eye tissues.

Public Comment by the International Council for Commonality in Blood Banking Automation (ICCBBA) 

Eoin McGrath, Executive Director, International Council for Commonality in Blood Banking Automation (ICCBBA) 

Eoin McGrath, a representative of the International Council for Commonality in Blood Banking Automation (ICCBBA), provides a verbal public comment regarding the current state of tissue transplantation. He notes that traceability can be challenging, particularly because a single donation event may result in the production of multiple items by multiple facilities that use different methods of collecting, processing, distributing, and applying materials. To increase traceability, ICCBBA supports use of ISBT 128 as a global standard for generating identification codes, labeling products, and transferring information. Adoption of a single standard facilitates data exchange and furthers the interoperability of electronic health information systems. McGrath notes that over 3,000 organizations in 75 countries use the ISBT 128 standard and several accrediting organizations endorse its use. Further adoption of the ISBT 128 standard would support biovigilance efforts.

Tissue Product Tracing During a Tissue-Derived Tuberculosis Outbreak

Kristen Marshall, PhD, MPH, Epidemiologist, CDC Epidemiology Field Officer Program, Colorado Department of Public Health and Environment (CDPHE)

Dr. Kristen Marshall described the Colorado Department of Public Health and Environment (CDPHE) response to an outbreak of donor-derived tuberculosis that occurred in 2021 and 2022 and involved products obtained from two separate donors. One donor produced 157 units of donor-derived materials (“Lot A”), 136 of which were implanted into 113 patients across 37 facilities in 20 states. Of these, two patients (referred to as “Patient 1” and “Patient 2”) received materials from facilities in Colorado. While Lot A was being investigated for potential contamination with tuberculosis, an additional patient, “Patient 3”, was reported to have received materials from a separate donor who was similarly diagnosed with tuberculosis. Materials produced by the second donor are referred to as “Lot B”.

In responding to the investigation regarding Lot A materials, Patients 1 and 2 were notified of the tuberculosis infection risk and began receiving treatment. Notably, Patients 1 and 3 developed tuberculosis while Patient 2 did not.

The CDPHE developed several hypotheses to aid in their investigation of these adverse events. These included 1) potential cross-contamination of products at the manufacturing facility, 2) the existence of a second donor infected with tuberculosis, 3) a mix-up of products at the transplant facility, and 4) contamination of surgical equipment with tuberculosis at the transplant facility.

CDPHE investigators rapidly proved hypothesis 1 to be insubstantial during the investigation as no product overlap was recorded. Similarly, hypothesis 2 was dismissed when investigators discovered via whole genome sequencing that the materials received by Patient 3 were genetically identical to Lot A materials – not Lot B materials. Furthermore, upon additional testing, Lot B materials continued to test negative for contamination with tuberculosis.

As part of their investigation, the CDPHE thoroughly reviewed patient medical information. The CDPHE examined patient risk factors, surgical notes, and post-operative notes to assist in determining whether the infection could have resulted from exposure at the surgical site or recovery at the transplant facility (e.g., within the operating room, post-acute care unit, or floor unit).

The CDPHE also conducted a site visit of the transplant facility to evaluate the facility’s tissue tracking processes from receipt of materials to implantation into the patient. The process includes initial receipt of materials within a foam cooler and scanning of identifying information. Operating room staff remove the cooler before transferring the product to the operating unit. Identifying information is once again scanned before products are placed in labeled bags in the tissue freezer for later use. The operating surgeon would request a specific product during a procedure, upon which the circulating nurse retrieves the product from the tissue freezer. The surgeon verifies that the circulating nurse retrieved the correct product, further processes the product (if needed) at the bedside, and implants the product into the patient. Finally, the circulating nurse records the identifying information again, completes the Implant Form, and inputs data into the facility tracking system.

The CDPHE observed that some products contain scannable information on the external packaging but not on the internal product vial, resulting in increased difficulty tracking products once they are within the operating room tissue freezer. Further, not all products have seals to confirm whether they are unopened.

Manufacturer information for the products in question states that if the products are left out of the freezer for longer than two hours prior to implantation, they should be discarded. The operating room manager and other staff members noted that the transplantation facility rarely returned products to the freezer once removed even if the product was unopened; staff only returned products to the freezer if the surgeon requested that they be returned. Further, staff reported that multiple products were sometimes present in the same operating room. Of note, however, is that various staff members gave contradictory reports. Together, information gleaned from this site visit indicated that product tracking procedures may have been insufficient.

While investigating the facility, the CDPHE examined the sterile processing department for potential gaps in their infection control procedures. The CDPHE observed gaps pertaining to instrument pre-cleaning, disassembly, soaking, brushing, and rinsing of surgical equipment. Staff were unable to adequately recall infection control procedures and likely did not receive adequate training, and the unit was generally understaffed. Each of these elements increased the potential for cross-contamination to occur. Five patients in addition to Patient 3 received Lot B materials from this facility. Upon follow-up, none of these patients had developed tuberculosis, indicating that cross-contamination was unlikely to be the source of infection. 

Continuing their investigation, the CDPHE observed an implantation surgery at this facility. They observed that some product containers did not have any seals to indicate whether they had previously been opened. Additionally, the CDPHE observed deviations in surgeon verification of product and submission of information following the procedure. Due to these deviations, the CDPHE was unable to track the final disposition of the product received by Patient 3 to confirm that a product mix-up had occurred. However, a product mix-up appears to be the most likely explanation for the development of tuberculosis in Patient 3 but not in Patient 2.

Following the investigation, this transplant facility engaged in corrective actions to reduce the risk of adverse events. These included reprocessing all surgical equipment and securing additional staff. Further corrective measures could include adopting a standardized method for tracking tissues and handling products, as well as additional educational opportunities on documentation and protocols. Improving tissue tracking can allow for easier identification of adverse events, treatment of patients, and reduce notification time following exposure of contaminants.

Discussion

Dr. Josephson asked whether costs could be a motivating factor in transplant facilities determining what product-types they will keep in supply and whether products will be returned to the operating room freezer after being unused within the operating room. Dr. Josephson also asked whether operating room staff monitored the temperature of products within the operating room and if that information was used to decide whether products could be re-entered into the operating room freezer. Dr. Marshall responded that the cost associated with these products was not determined, however, transplantation facilities likely take that into account when determining whether to return products to the operating room freezer. Further, the temperature of the product was not recorded on any of the implant forms reviewed.

U.S. Regulations on Blood Traceability, Lookback and Adverse Reaction Reporting

Anne Eder, MD, PhD, Director, Office of Blood Research and Review (OBBR), Center for Biologics Evaluation and Research (CBER), FDA

The blood supply industry is regulated by Office of Blood Research and Review (OBBR), the 21 CFR, and 42 CFR. OBBR is responsible for the review of blood licensing applications, applications for the collection and manufacture of blood and blood components, new drug applications (e.g., anticoagulants) that can be applied to blood bags, and devices related to biologics (e.g., screening tests, confirmatory tests, and pathogen reduction devices). Additionally, OBBR conducts research and develops both policy and guidance materials to support adherence to regulations and improve patient safety. The 21 CFR describes regulations under the purview of the FDA for blood centers and pertains to the traceability, lookback requirements, and adverse event reporting of blood and blood-based products. The 42 CFR describes regulations under the purview of CMS and describes the hospitals’ responsibilities. This presentation centered on regulations described within 21 CFR part 606 describing Good Manufacturing Practices (e.g., identification, traceability), 21 CFT part 610 describing testing, and their counterparts described in 42 CFR where applicable.

Part 606 describes the standard operating procedures that blood establishments are required to maintain and follow. Procedures include steps in the collection, processing, compatibility testing, storage, and distribution of blood and blood components. Further, Part 606 stipulates that blood facilities must maintain a system capable of relating products to their donor and blood or blood components from the donor to their final disposition.

Further regulations described in 21 CFR require that blood facilities be able to perform lookbacks if blood or blood products have the potential to test positive for HIV or Hepatitis C. When a potential HIV or Hepatitis C contamination has been identified, blood components collected within the past 12-months before the most recent nonreactive screening test or reactive viral detection test (e.g., nucleic acid test) must be identified for quarantine and consignees must be notified. If products continue to test positive for infectious materials, recipients must be notified of the potential transmission event. Similarly, 42 CFR requires that hospitals notified of contaminated materials must discard any related products, notify recipients, and keep records of the event for at least 10 years. Furthermore, if the donor is deceased when the infection is identified, regulations require that the donor’s physician or family be notified of the potential infection.

A study performed by the American Red Cross (ARC) using data from 2003 to 2010 highlighted the importance of both lookbacks (i.e., identifying recipients from a known donor) and tracebacks (i.e., identifying products related to a donor from a known recipient). During the study period, 39 HIV-positive donors were identified via lookbacks and additional 134 patients were identified via traceback following hospital reports of a potential contamination event.

Part 606 of the 21 CFR also describes requirements for reporting adverse events and fatalities related to blood and blood products. These include the requirement that blood centers maintain records of complaints and adverse events and conduct investigations of each adverse event. Fatal adverse events must be reported to the FDA within 7 days of the fatality. These include fatalities resulting from transfusion with incompatible blood types as well as any deviations that occur.

Reports of deviations required by 21 CFR Part 606, including those resulting in fatal and non-fatal adverse events, serve as a source of national hemovigilance data. For example, the FDA issued guidance for 14 states and the District of Columbia with emergent or endemic Babesia infections requiring that donated blood be tested for potential contaminants. Donors that test positive for Babesia are deferred for a minimum of two years post-positive test. The implementation of 21 CFR 606, in addition to lookback and traceback efforts to identify high-risk donors, resulted in a steady decrease of Babesia biomarkers within the national blood supply.

Discussion

Dr. Goodrich relayed an anecdote of a physician comparing the probability of infection with HIV resulting from a blood transfusion to that of being struck by lightning, which was received poorly by a patient. He continued to state that perfection is impossible to attain, but the drive to improve patient safety has led to improvements within the blood supply. He noted differences in the importance of informed consent within the tissue transplantation and blood supply industries. Further, the tissue transplantation industry has a high potential for the products form one donor to be implanted in numerous patients, while the blood supply industry is more limited in the products obtained from one donor at a discrete point in time (e.g., one donation event). Dr. Anne Eder agreed with the points proposed by Dr. Goodrich and added that a timely response and ability to perform lookbacks and tracebacks is important for supporting patient safety.

Dr. Josephson added that a substantial difference between blood and tissue systems is the centralization and decentralization of these systems within a hospital. Hospitals often rely on one centralized blood system while tissue systems are often decentralized and managed by several people or hospital units. Further, there are fewer blood collections facilities than tissue collection or processing facilities – increasing the variability of systems among tissue centers.

Solid Organ Transplant Lookback, Traceability, and Disease Transmission Reporting Requirements

Stephanie Pouch, MD, MS, FAST, FIDSA, Chair of the Organ Procurement and Transplantation Network (OPTN) Disease Transmission Advisory Committee (DTAC)

In 2005, the CDC and the Organ Procurement and Transplantation Network (OPTN) commissioned the Disease Transmission Advisory Group (DTAG) to receive and report on potential donor-derived disease transmission events from whole organ transplantations. DTAG later evolved into Disease Transmission Advisory Committee (DTAC), an independent committee. The DTAC currently serves as an organ biovigilance system which has been charged with considering issues related to disease transmission through organ transplantation.

The DTAC collects information related to transmission events, including confirming cases of donor-derived infections, and uses this information to identify gaps in communication and assess risks related to donor-derived disease transmission during donation and transplantation. The DTAC also serves to educate the transplantation community to inform the prevention of and response to future transmissions. Further, the DTAC advises the OPTN Board of Directors in their development of patient safety policies.

To accomplish these activities, the DTAC includes members from diverse specialties involved in all aspects of organ transplantation, such as infectious disease specialists, Organ Procurement Organization (OPO) professionals, surgeons, and laboratory specialists. The DTAC includes members of the OPTN, Office of Blood, Organ, and Other Tissue Safety (BOOTS), FDA, and HRSA Division of Transplantation, among others.

Organs procured and distributed within the United States are assigned a unique alphanumeric identification code accessible by transplant centers and OPOs. These codes serve to link donors with organ recipients, providing a means of communication to relay donor results, notify OPOs and transplant centers should an adverse event occur, and report adverse events to the OPTN.

As part of the requirements outlined by DTAC, facilities are required to report pathogens of special interest (e.g., anthrax, tick-borne illnesses, tuberculosis, and HIV), cancerous malignancy, and other information relevant to patient safety. Reports are required to include information such as donor serologies, microbiology assessments, and histopathology findings. Adverse events suspected to result in patient fatalities due to infection or malignancy must be reported to the OPO or hospital and submitted through the OPTN Improving Patient Safety Portal within 24 hours of the event.

Extra vessels, described as blood vessels recovered during the donation process but not connected to the organ, are also subject to OPTN regulations. These materials may be stored for up to 14 days post-recovery, unless they are recovered from donors with HIV, hepatitis B, or hepatitis C, in which case they cannot be stored. Transplant organizations must report the disposition of extra vessels to the OPTN within seven days of their use, distribution, or destruction.

After a report is submitted to the Improving Patient Safety Portal, the DTAC patient safety team processes the information. The team also prepares emails and case summary documents and updates the case database. While an investigation is ongoing, DTAC will facilitate case review and communications between OPOs and transplant centers and collect initial and follow-up information from organ recipients. Finally, DTAC will review the case and make adjudications. Approximately 350 cases are reviewed annually. Cases are assigned a classification reflecting the probability that the adverse event resulted from donor-derived transmission. The classifications include “proven”, “probable”, “possible”, “intervention without documented transmission”, “unlikely”, and “excluded”. Classifications other than “unlikely” or “excluded” are also assigned a severity rating, ranging from “death” to “non-severe”.

A review of aggregate data acquired from 2008 to 2017 highlights the importance of DTAC’s biovigilance. Within this timeframe, 2,185 reports were submitted to DTAC. Of these, approximately 15 percent were classified as either “proven” or “probable” donor-derived transmission events. The most common infectious agents included viruses, bacteria, and fungi.

The number of reports submitted has been increasing, reaching a peak in 2022 with 590 cases reported that year. Approximately 5 percent of those cases were classified as either proven or probably donor-derived transmission events. Overall, data indicates that only 0.3 percent of all organ recipients that year were affected by a donor-derived adverse event, with lung-recipients being disproportionally affected by donor-derived diseases. However, as this is a passive reporting system, under-reporting of adverse events is likely to occur.

Information gathered by the DTAC is used to develop educational materials and inform policy decisions. As guidelines are revised over time, including Public Health Service Guidelines, the DTAC has been able to provide relevant information to improve public safety guidelines. This is reflected in the 2020 Public Health Safety Guidelines, which were informed by joint DTAC and CDC efforts to evaluate meaningful testing requirements. The risk criteria for acute HIV, hepatitis B, and hepatitis C transmission were reduced from 14 to 10 and the window to consider elevated risk criteria was reduced from 12 months to 30 days prior to organ recovery. These reductions served to increase organ utilization while minimizing risk of disease transmission.

Additional policy changes were observed in response to the COVID-19 pandemic. Following OPTN and DTAC guidance, OPOs were required to test lower lung samples for COVID-19 prior to lung transplants. This resulted in a dramatic reduction of donor-derived COVID-19 transmission events while maintaining organ utilization.

The DTAC is continuing to analyze patient outcomes and best practices to better support patient safety related to prevention of additional infections, such as strongyloidiasis, Mpox, tuberculosis, and additional diseases relevant to public health.

Discussion

Dr. Glenn Ramsey described an adverse event in which the patient had received both a blood transfusion and organ transplantation and the adverse event was later determined to have resulted from the blood transfusion. He also noted that cross-communications between blood centers, organ centers, and tissue centers may serve to identify potential sources of donor-derived infections rather than have overseeing bodies function independently.

Dr. Josephson noted that the structure surrounding the investigation of donor-derived infections following organ transplantation is not as robust among tissue transplantation investigations. Brubaker noted that efforts had been made in the past to establish a robust infectious disease investigation system. Currently, hospitals are not mandated to report adverse event information following a tissue transplant to the same degree that hospitals are mandated to report adverse events following organ transplants. Barnes noted that the AATB is a voluntary association that strives to share best practices and codify those in the standards of accreditation, however, reporting could be improved by incorporating end-users.

Barnes noted interest in the frequency of donor-derived malignancy and asks whether deceased donors are regularly autopsied to identify potential malignancies. Dr. Stephanie Pouch noted that not all deceased donors receive an autopsy, but autopsies are beneficial in identifying malignancies.

Dr. Goodrich asked about the timeframe from receiving a report of an adverse event and the DTAC adjudicating the case. Dr. Pouch noted that the process can require a variable amount of time, and that 45 day follow up with recipients is typically preferred before the case is adjudicated. That timeframe can be decreased in cases of public health significance where the CDC is also evaluating the case.

CMS Regulatory Oversight Over Healthcare Facilities, Infection Control Requirements: Opportunities for Enhancing Tissue Safety

Diane Corning, RN, JD, Health Insurance Specialist, Office of Clinical Standards and Quality, Clinical Standards Group, Centers for Medicare & Medicaid Services (CMS)

The Clinical Standards Group is responsible for the development, promulgation, revision, and interpretation of the Conditions of Participation (CoPs), Conditions for Coverage (CfCs), and requirements for providers and suppliers engaged in Medicare and Medicaid programs. These requirements must be met for Medicare and Medicaid participating providers and suppliers to receive reimbursements. Additionally, they ensure that Medicare and Medicaid participants provide high quality care, protect individuals receiving services, and contribute to quality improvement.

CMS has the authority to regulate hospitals, critical access hospitals, and ambulatory surgical centers that handle tissues. While the FDA is responsible for regulating tissues, CMS can regulate how these agencies manage tissues received by their facilities. Regulations and safety requirements can be addressed as requirements for patient records, surgical services, or infection prevention and infection control.

CMS has requirements for surgical services provided by hospitals, but not those provided by critical access hospitals or ambulatory surgical centers. Requirements for hospitals include producing an operative report which describes operative techniques and findings and lists any tissues that were removed or altered. These reports are required to be written immediately following surgery and must be signed by the operating physician. However, there is no requirement for hospitals to track tissues received or those implanted within a patient.

Hospitals, critical access hospitals, and ambulatory surgical centers all have regulations pertaining to infection control. Hospitals and critical access hospitals are required to have facility-wide programs for the surveillance, prevention, and control of hospital-acquired infections and other infectious diseases. These requirements include the designation of an infection preventionist but does not specifically mention tissue safety or donor-derived infections. Ambulatory surgical centers are similarly required to maintain an infection control program. Additionally, they are required to maintain a plan of action for preventing, identifying, and investigating infections and communicable diseases, including implementing corrective measures following an adverse event.

Overall, CMS has limited authority to require tissue regulations from health care systems. They are authorized to regulate healthcare facilities; however, they cannot mandate requirements pertaining to the tissues themselves because that falls under the purview of the FDA. Nonetheless, CMS is concerned about public safety; CMS representatives look forward to collaborating with federal partners to improve tissue biovigilance.

Discussion

Dr. Josephson asked whether CMS regulations or methods of regulating stem cells can be applied to tissues. Dr. Galel replied that a similar mechanism to what she is proposing may be related to deemed authority. Dr. Galel provided the example of the Association for the Advancement of Blood and Biotherapies (AABB) having the authority to perform inspections to ensure that facilities are complying with requirements. Adopting this method would not rely on establishing new requirements, rather, it would grant CMS or other organizations the authority to ensure that health care facilities are adhering to best practices. Dr. Ramsey clarified that accrediting agencies are required to meet basic CMS requirements and can enforce best standards of practice and good manufacturing practices. Proposing additional requirements for an organization to be accredited could be impactful for improving tissue biovigilance.

Dr. Hermelin described that hospitals that want to have a surgery center are required to have transfusion services on site. The transfusion services are inspected by government agencies and accrediting organizations. Dr. Hermelin asked whether similar requirements and inspections could be required for tissue transplantations to occur.

How Do Tissue Establishments Conduct Product Tracking?

Melissa Greenwald, MD, FAST, Chief Medical Officer, American Association of Tissue Banks (AATB)

American Association of Tissue Banks (AATB) is a professional nonprofit that serves as a standard setting organization for the promotion of safe tissue transplantation. Their membership includes tissue processors and tissue recovery organizations, hereafter described as tissue banks. Most large tissue processors and OPOs are currently AATB-accredited, and most tissues distributed for transplantation in the United States are from AATB-accredited facilities. However, AATB does not oversee clinical facilities.

AATB initially released standards guidelines in 1984 and continues to revise their guidelines to improve patient safety outcome. Their standards address aspects of quality management, donor eligibility and screening, tissue recovery and processing, as well as tissue storage and distribution. These include provisions for product traceability and conducting product retrieval and recall.

The AATB Standards Committee receives input from multiple sources when developing and revising standards. Input comes from federal agencies such as the FDA and CDC, state agencies such as the New York State Department of Health, other accrediting agencies such as the Eye Bank Association of America (EBAA), and from other sources as needed. Revised standards are distributed to AATB members for comment, after which the standards are shared with the AATB Board of Governors for approval. Standards are designed so that complying facilities are also in compliance with federal regulations. Additionally, tissue banks are inspected every 3 years and audits are submitted to tissue banks that are not in compliance with 21 CFR part 1271 regulations.

Dr. Melissa Greenwald provided an overview of the tissue transplantation system. A variety of tissues may be recovered from a single donor (e.g., ocular tissue, organs, and bone) and multiple agencies may be involved in the tissue recovery process. Once recovered, tissues may be distributed to multiple tissue processing organizations. Several tissue distribution intermediaries may be involved before tissues are accepted by a healthcare facility, after which, tissues may be used in a variety of clinical applications. The variety of organizations involved, differences in accreditation standards among these organizations, and wide variety of tissue use cases increase both the difficulty and the importance of maintaining a system capable of tracking and tracing these products.

Tracking and tracing tissue products is integral to biovigilance activities, performance of product recalls, and for informing general business practices. Tissue tracking and tracing systems improve patient safety by allowing for the collection and evaluation of information that can be used to reduce unexpected or undesirable outcomes, communicating occurrences of disease transmission, and effectively recalling contaminated products. Further, these systems inform the supply chain and asset management to improve usage and general healthcare practices.

A successful tissue tracking and tracing system involves several key components. First, a single unique donor identifier should be applied to a product. Second, product information should be recorded at every step of the process, from recovery to final disposition. Finally, the system should enable patient monitoring and reporting of adverse events over an extended timeframe.

AATB standards reflect these key components. The standards require that facilities have a quality assurance program capable of performing traceability, assisting recalls, and monitoring inventory management. Documentation requirements ensure that donor records, as well as distribution records, are maintained, and that data are collected from tissue recipients. Finally, the standards require that tissue tracking and tracing systems be capable of maintaining information for and assisting in reporting adverse events and recalls.

The tissue tracking and tracing process is initiated when a clinician identifies that a tissue recipient may have experienced an adverse event. The clinician or healthcare staff member is responsible for notifying tissue distributors or processors that provided the tissue in question. Processors then investigate the tissue product and, if the processors still suspect that the tissues contributed to an adverse event, notify the facility’s accrediting organization, the FDA, and other organizations or consignees that have interacted with materials received from the initial donor. Each facility that received materials from the initial donor is then responsible for communicating the adverse event to their downstream facilities (e.g., healthcare facilities and tissue banks). Often, this results in a complex notification system involving both tracebacks and lookbacks as adverse events are reported and additional healthcare facilities or tissue banks are identified.

These complexities can result in a lengthy timeline between the initial onset of an adverse event and identification of the final disposition of materials obtained from the same donor. Further, these complexities can result in an inability to track all relevant tissues to their final disposition, impacting patient safety. Examples of donor-derived infections of hepatitis C in 2001 and 2011, rabies in 2004, Mycoplasma hominis in 2015, and tuberculosis in 2021 are highlighted as examples of adverse events in which not all tissues could be tracked to their final disposition in a timely manner.

Several key challenges contribute to the difficulty of tracking and tracing tissues to their final disposition. First, tissues retrieved from a single donor may be used in products with different regulations (e.g., HCT/Ps and medical devices). Second, the lack of a universal system for assigning identifiers to tissues or donors results in products or donors being assigned multiple codes, ultimately leading to increased complexity when performing lookbacks. Third, implant cards may be returned with incomplete information, or not returned at all. Fourth, use of passive surveillance systems can increase the lag time in recognizing and reporting adverse events. Finally, the wide variety of end-users and applications for tissues results in clinicians and other health care providers having various levels of knowledge regarding related adverse events, further increasing recognition and reporting time.

AATB is currently developing a data collection system to combat these challenges. The system will be able to use tissue identifiers to identify if tissues have been procured from a recalled donor, track tissues in real-time as they move between facilities, and perform both lookbacks and tracebacks. The system will also be able to inform scientific research, monitor tissue usage, and provide meaningful metrics for the safety and availability of tissues. However, this system will rely on interoperable health records and their ability to maintain tissue identifiers.

Dr. Greenwald adds that AATB has revised their requirements and guidance information in response to the recent outbreaks of donor-derived tuberculosis. Following these outbreaks, AATB has adopted new evidence-based criteria for determining donor eligibility and are engaging leadership throughout the tissue industry to continue supporting the improvement of their standards. Finally, the AATB Physician’s Council has developed working groups to assess challenges related to sepsis and improve training and education for medical directors. 

Discussion

Dr. Goodrich requested clarification regarding the proportion of tissue banks that are accredited by AATB. Dr. Greenwald responded that 125 tissue banks are accredited by AATB. AATB primarily accredits musculoskeletal transplant-type tissue banks, although there are tissue banks which procure or process other types of tissues as well (e.g., ocular tissue, reproductive tissue). Registering for accreditation with AATB is a voluntary process and tissue banks may elect not to use this service. Barnes added that some organizations that do not manufacture tissues may not value becoming an AATB-accredited organization, rather, those organizations may elect to partner with AATB-accredited manufacturers or procurers. Barnes indicated that AATB is working to convince OPOs of the value of becoming an AATB-accredited organization as it would improve the quality of the overall supply chain and patient safety.

Dr. Pruett asked what percentage of the U.S. tissue supply is distributed by AATB-accredited organizations as it would assist in determining the impact of requiring AATB-accredited facilities, or other accrediting bodies, to adhere to specific requirements (e.g., assigning a single donor identifier per accrediting organization). Dr. Greenwald indicated that this can be a topic for further discussion as it is currently unclear how donor identifiers are determined by tissue facilities involved. Tissues collected from organ donors are assigned a UNOS identifier, however, those identifiers are often not entered into the tissue establishment. Recent reports have indicated that UNOS identifiers may be considered as personally identifiable information which would make them unable to be used for anonymous tissue tracking. Further, it is unclear how many tissue products are distributed within the United States as the current tissue biovigilance system is insufficient to generate reliable estimates.

Dr. Pruett asked Dr. Basavaraju if he is aware of the proportion of adverse event investigations performed from AATB-accredited facilities. Dr. Basavaraju does not believe that investigations request information about accrediting organizations. Barnes added that facilities accredited by different organizations, and nonaccredited facilities, have different standards for determining donor eligibility, tissue processing, and infection mitigation strategies.

Dr. Michelle Kameka described that there is a desire to move towards an efficient and linear tracking and tracing tissue biovigilance system. The current system is fragmented with missing information, incorrect information, and non-interoperable surveillance systems. Dr. Kameka indicated that while it may be difficult to define and mandate a single process to ensure tissue biovigilance, ACBTSA members should not allow the desire for perfection to hinder positive, if flawed, developments.

Diane Wilson indicated that unique identifiers had been applied to tissue products that were later investigated. Rather, the issue is that tissues that are transferred out of tissue banks (e.g., to consignees, to end-users) become difficult to track. A gap exists in the record keeping of consignees and end-users that increases the difficulty of maintaining tissue biovigilance. Dr. Josephson agreed with Wilson and stresses that those tissues that are difficult to track become an important focus as they can contribute to the occurrence of donor-derived infections and disease transmission. She added that transitioning towards adopting interoperable systems would improve data collection and maintenance.

Dr. Josephson questioned current donor eligibility guidelines, providing the example that an 86-year-old person is unlikely to be an ideal donor of bone tissue. She indicated that more stringent criteria for donor eligibility would reduce the number of contaminated tissue products.

Dr. Gorlin indicated that the current tissue biovigilance community is dependent on a few highly-skilled individuals and expresses concern about the reliance on individuals for the maintenance of a communication system and knowledge base. Dr. Greenwald described that the AATB’s medical director education and training working group is seeking to develop a platform for emerging infectious disease information for the reference of medical directors.

Brubaker requested clarification on whether the AATB requires implant cards to be completed and returned. Dr. Greenwald responded that the AATB requires that implant cards are provided with every tissue product. Brubaker indicated that previous surveys indicated that AATB accredited facilities almost always provided an implant card alongside every tissue product, however, the rate of consignees and end-users that returned completed implant cards was very low.

Dr. Goodrich agreed that the issue of tissue biovigilance is important. He described that individuals who have previously received products that may have been contaminated, and the families of those individuals, are highly impacted by issues of adverse events and tissue biovigilance.

Day 1 Wrap-up and Adjournment

Dr. Cohn thanked the presenters and members of the ACBTSA for their efforts and willingness to donate their time and expertise to improve the tissue biovigilance system. She noted that two types of presentations were delivered today: those that describe regulations and oversight of blood, tissue, and organ systems and those that highlight examples of gaps within blood, tissue, and organ systems and the effect of these gaps on public health. Dr. Cohn thanked Brubaker and Dr. Pruett for their leadership within the Tissue Biovigilance Subcommittees. Dr. Cohn requested that ACBTSA members review the recommendations and related materials before the second day of the meeting, and that they consider patient safety and actionability during their review. Recommendations drafted by the four Tissue Biovigilance Subcommittees were presented for discussion and voting during the second day of the meeting.

Day Two Welcome and Opening Remarks

Dr. Cohn welcomed ACBTSA members to the public meeting and provided an overview of the agenda. Berger conducted roll call to confirm a quorum.

Dr. Pruett described tissue biovigilance recommendations previously proposed by the ACBTSA. Recommendations to improve traceability, identify tissues produced, identify the final disposition of tissues, identify and report adverse events, and promote patient informed consent procedures had been proposed in November 2009 and April 2015, however, these recommendations had not been enacted. The Tissue Biovigilance Subcommittee had been established in response to donor-derived tuberculosis outbreaks and discussed issues of tissue source, tissue processing, tissue end-user or consignee receipt and use, and tissue recipient adverse events or reactions. The subcommittee has generated a series of recommendations for the ACBTSA Committee’s review.

Discussion on Recommendations

Brubaker, Dr. Cohn, and Dr. Pruett led the ACBTSA Committee in a review and live revision of proposed recommendations that were made available on the ACBTSA website. Recommendations were provided by the Tissue Biovigilance Subcommittee and comments received during the public comment period were incorporated as revisions.

Tissue Source Recommendations

Recommendations Originally Proposed

Recommendation 1:

To close gaps and to promote collection of information that could inform donor eligibility policy when screening donors of cells and tissues, standardized donor medical history interview forms and related tools should be developed and recommended in guidance issued by professional societies and regulatory authorities. 

Recommendation 2:

To optimize control of contamination, effective practices surrounding cell and tissue recovery/acquisition procedures should be identified and standardized across industry. 

Recommendation 3:

To inform cell and tissue donor screening policies, information collected from investigations and adjudication processes involving reports of probable transmission of disease to organ or tissue recipients must be disseminated widely by all groups involved in investigations. 

Discussion on Tissue Source Recommendations

Donor History Questionnaires

Dr. Josephson asked for further information regarding existing donor screening policies, noting that there may be gaps in determining donor eligibility. Dr. Cohn responded that medical experts should be involved in revision of donor eligibility guidance information. Ideally, a panel of experts would be assembled to develop an appropriate donor history questionnaire.

Dr. Galel provided further information on the blood donor history questionnaire. Currently, blood centers are not required to use a specific blood donor history questionnaire; rather, the AABB and FDA have approved a questionnaire, and alternative questionnaires require FDA approval before use. Additionally, the blood donor history questionnaire includes a flow chart to provide guidance on donor eligibility and processing required to make the donated blood acceptable for use. Dr. Galal suggested that requiring FDA approval for tissue donor history questionnaires could motivate tissue banks to use a pre-approved questionnaire.

Dr. Eder further described differences between the oversight of blood centers and tissue banks. The AABB continuously develops their donor history questionnaire to ensure that it is up to date with FDA regulations and patient safety concerns. While the AABB’s donor history questionnaire is not required to be used by blood banks, blood banks tend to use it to ensure that they are following FDA regulations. Dr. Eder confirmed that review procedures related to manufacturing blood products are reviewed during licensure and inspection of facilities that transfer products across interstate lines to ensure compliance with FDA regulations. Facilities that collect, manufacture, and transfuse blood and blood products within a single state are not required to have their procedures reviewed.

Several committee members agreed that requiring a uniform, FDA approved questionnaire for tissue donor eligibility determinations would improve donor eligibility determinations and overall tissue biovigilance.

Brubaker noted that the Universal Donor Risk Assessment Interview (UDRAI), which has already been approved by the FDA, could be used as a uniform, FDA approved questionnaire. The UDRAI was developed and reviewed by federal authorities and stakeholders; this review included an evaluation of cognitive interviewing techniques by the National Center for Health Statistics. Brubaker continued to describe the importance of universal data collection for informing policy development. While use of the UDRAI is voluntary for tissue banks, Barnes noted that it is used among AATB-accredited tissue banks and their partners. Barnes continued to say that the AATB is working towards updating the UDRAI to reflect recent developments in AATB guidance. Further, the AATB is positioned to rapidly respond to emergent infections and release updated guidance annually. Currently, the EBAA and the Association of Organ Procurement Organizations are not involved in revising the UDRAI. Committee members noted that the committee should consider integrating FDA-approved tools such as the UDRAI into the recommendation language.

Additional committee members noted that reliance on tissue donor histories may be insufficient as patients are often unable to communicate their medical histories or proxy historians may have incomplete information. The committee suggested that improved guidance regarding testing for potential contaminants may improve patient safety. However, as there are limited data available describing the quality of tissue donors, it is difficult to quantify associated risks and develop meaningful guidance materials. Further, adopting a central data repository for donor information could improve information access.

Barriers to Donor Information Collection

Dr. Hermelin noted that there may be gaps in how donors are identified and followed-up with. Currently, potential donors are identified when individuals register as organ donors and there is no follow-up for contacting registered individuals. Data collection may occur if organ donors donate blood, in which case they are required to complete a donor history questionnaire. Finally, donor information is collected upon admission to a hospital. Dr. Hermelin suggested that identifying donors and obtaining donor information post-mortem is not ideal and may contribute to donor-derived infections. Collecting donor history information during the donor’s lifespan may contribute to an improved donor population. Brubaker clarified that gaps related to when donor information is collected were not identified and recommendations on this topic are not proposed at this time.

Dr. Basavaraju asked Brubaker whether the Public Health Service Act describes the amount of guidance that the FDA can provide regarding donor information collection. Brubaker responded that the Tissue Biovigilance Subcommittee could review the topic further. However, he expresses concern that the FDA may not currently have the authority to mandate that tissue banks use specific forms.

Dr. Sarah Barnhard noted that federal oversight and registration requirements are integral to the functioning of hospital-based transfusion centers. These transfusion centers discuss federal regulations frequently, and their quality management systems are designed to ensure compliance with federal regulations. She questioned whether the Tissue Biovigilance Subcommittee has determined the potential impact of requiring a standardized donor eligibility assessment. Brubaker responded that tissue banks are required to register and list tissue products that could be produced by their facilities. Dr. Bennie Jeng noted that the EBAA can accurately report on the exact number of donors and transplants that they oversee. He added that it is important that each organization have the ability to track this information and be able to communicate with one another.

Dr. Paul Ness noted that cases of donor-derived infections have been related to materials retrieved from both living and deceased donors. Therefore, increased specificity within donor history interview forms and related tools for both living and deceased donors is needed to identify potential risks of donor-derived infections.

Dr. Hermelin noted difficulties in determining whether tissue products are under the purview of section 351 or section 361 of the Public Health Service Act. Dr. Marilyn Levi added that there are clear guidelines and eligibility assessments used for solid organ donations. She stated that organ and tissue suppliers share similar public health concerns and should have similar regulations and guidance procedures.

Designating Authoritative Organizations to Act on Recommendations

Dr. Goodrich commented that the recommendations should specify the organizations and agencies that will be responsible for enacting them. He expressed concern that if acting bodies are not specified, the recommendations will not be implemented or will be implemented in fragments rather than as a unified effort. Dr. Basavaraju and Brubaker suggested that the recommendations could designate an authoritative organization that will convene meetings of industry or professional associations to engage in the development of guidance materials (e.g., donor eligibility assessments).

Overarching Goals of Recommendation Revisions

Dr. Cohn summarized several talking points from the discussion. She indicated that common discussion points included designating authoritative organizations to act on the recommendations and increasing the specificity of actions being recommended. To encourage uptake of the UDRAI or equivalent tools, Dr. Galel suggested that the group propose mandatory FDA approval for donor eligibility tools.

The ACBTSA committee revised the recommendations proposed by the Tissue Source Working Group to improve actionability and emphasize the importance of these recommendations. This includes proposing involvement of named organizations that oversee relevant health care facilities (e.g., AATB, EBAA, AOPO, FDA). Further, the recommendations were revised to indicate that actions must be performed to improve tissue biovigilance, data collection, and the availability of information.

Revised Recommendations and Voting

Recommendation 1:

ACBTSA recommends that the following be required by professional associations (e.g., AATB, EBAA, AOPO) and recommended in guidance recognized by FDA: 

1. To close gaps and to promote collection of information that could inform donor eligibility policy when screening donors of cells and tissues, standardized donor medical history interview forms and related tools must be developed and recommended. 
2. To optimize control of contamination, effective practices surrounding cell and tissue recovery/acquisition procedures must be identified and standardized across industry. 

Dr. Cohn motioned to vote on Tissue Source Recommendation 1 as revised. Berger seconded the motion. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 2:

To inform cell and tissue donor screening policies, information collected from investigations and adjudication processes involving reports of probable transmission of disease to organ or tissue recipients must be disseminated widely to all groups involved in investigations. Deidentified information would also be publicly available. 

Dr. Cohn motioned to vote on Tissue Source Recommendation 2 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Tissue Processing Recommendations

Recommendations Originally Proposed

Recommendation 1:

To optimize cell and tissue product traceability from donor to recipient and back to the donor, the use of electronic systems must be required by health authorities; electronic health records (EHR) must have functionality to accommodate a variety of long, distinct identification codes assigned to products; and manufacturers' requests for product disposition information from end-users should be required. 

Recommendation 2:

To overcome bioburden assessment and process validation procedures that are inadequate for detecting contamination of tissue products that pose the greatest risk to recipients, microbiological process validation and surveillance programs must be effective, standardized by experts, and followed by industry. 

Recommendation 3:

To improve accountability and reduce variability that can affect recipient safety, donor eligibility determinations made by responsible persons should be independently monitored and noncompliance formally addressed. 

Recommendation 4:

To inform national standards, recommendations, and policies, cell and tissue donor screening experiences, donor testing outcomes, and data regarding use of products must be periodically collected, formally analyzed, and published every 2-3 years. 

Discussion on Tissue Processing Recommendations

Dr. Gorlin requested clarification as to whether Recommendation 1 would require the use of electronic implant cards rather than paper implant cards. Brubaker clarified that Recommendation 1 was developed to broadly indicate that EHR must be capable of accommodating distinct identification codes. Dr. Galel added that managing physical implantation cards increases the time required to identify people who may be affected by adverse events. She elaborated that some cards are returned without patient identifying information.

Dr. Meghan Delaney asked whether the committee would consider recommendations directed towards preventing donor-derived tuberculosis. Dr. Greenwald responded that the AATB initiated a Physician’s Council to review risks associated with donor-derived tuberculosis. The Physician’s Council identified that the tissue industry has substantial criteria specific for tuberculosis. The Physician’s Council is also reviewing aspects of the tissue industry related to sepsis and training for medical directors. Brubaker added that the FDA is currently developing guidance that includes considerations for tuberculosis and sepsis.

Dr. Barnhard requested a revision of Recommendation 1 to indicate that EHR should be in alignment with FDA guidance and that software vendors should develop a system similar to the Blood Collection Centers Solutions (BECS). She also suggested that Recommendation 1 establish a standard for documentation at the point of implantation. Dr. Galel added that the Epic EHR system can accommodate unique donor identifier codes, indicating that some software vendors are including tissue biovigilance capacities within their products.

Dr. Galel noted that there are significant similarities between Tissue Processing Recommendation 1 and recommendations proposed by the Tissue End-User/Consignee Receipt and Use Working Group. Dr. Galel proposed moving Recommendation 1 to the Tissue End-user/Consignee Receipt and Use recommendations to improve overall continuity.

Barnes requested further context as to how Recommendation 2 was developed. Brubaker responded that Recommendation 2 was developed to address the limitations of testing tissue samples with molecular or culture methods. Barnes described his experience with FDA inspections and process validation reviews, indicating that methods of bioburden assessment are regulated and required to meet FDA guidelines. Brubaker indicated that tissue banks are selected for FDA inspection using a risk-based approach; some facilities may not be inspected for an extended period, which may contribute to deviations being unidentified for extended periods of time. The Tissue Processing Working Group identified that AATB has developed guidance documentation describing bioburden assessment processes, but tissue banks are not required to follow AATB’s guidance.

Dr. Gorlin suggested revising Recommendation 2 by replacing “be effective” with “mitigate risk” to clarify that all the processes listed must be revised to minimize risk, be standardized by experts, and be used by the tissue industry.  

Dr. Basavaraju implored the committee to consider the breadth of tissue biovigilance rather than narrowly focusing on issues related to tuberculosis. Current surveillance methods are insufficient to fully understand risks associated with viable cells (e.g., infection transmission), which are contained in tissue and tissue products. Therefore, he requested that the recommendations support additional surveillance programs and method suitability testing to increase understanding of emergent infections and additional public health concerns.

Stacy Sime indicated that the blood industry uses a standardized approach for monitoring biovigilance because it is required by accrediting organizations. Sime notes that blood supply and tissue supply industries are slow to change and prone to adopting the path of least resistance. Repercussions (e.g., more frequent FDA inspections) could serve as a motivation for blood supply and tissue supply industries to adopt new standards.

Dr. Josephson recalled an event in which the blood supply industry responded to cases of platelets contaminated by bacteria. The response was initiated by individuals who wrote letters to blood supply and government representatives which conveyed the importance of responding to the contamination and the overall need to improve biovigilance to protect end-users. Dr. Josephson compared the response to that event with the response to donor-derived tuberculosis outbreaks, indicating that a similar federal and industrial response to improve tissue biovigilance protocols is required. 

Dr. Levi described challenges associated with testing tissues for tuberculosis. These challenges include lengthy time to complete assays and difficulty detecting tuberculosis in non-acute stages. Dr. Levi indicated that detection is limited by available testing procedures and that improving communication would be a meaningful and feasible method of improving tissue biovigilance. Brubaker responded that some tissue products have a shelf-life that could accommodate longer timelines required for more sensitive culture testing.

Barnes indicated that a similar occurrence of contaminated tissue being accepted into the tissue banking system could happen again. He noted that the use of validated processes alone is not sufficient to overcome deviations from said processes.

Dr. Gorlin requested clarification on whether Recommendation 3 would require that two or more people review donor eligibility determinations before tissues are released, or whether it would require post-hoc audits of some donor eligibility determinations to determine if guidance was followed. Wilson responded that Recommendation 3 was developed with the intent to require that two people review donor eligibility determinations before tissues are released. Wilson elaborated that the intent was to require that a physician or other responsible person with medical knowledge review donor eligibility determinations. Recommendation 3 was revised to clarify that two persons should review donor eligibility determinations before tissues are released.

Dr. Josephson requested that Recommendation 3 specify how donor eligibility determinations should be made. Dr. Josephson noted that in the blood industry, one responsible physician determines donor eligibility. This process ensures that there is one person responsible for liability. She suggested that the process of acquiring information and providing it to the medical director be revised to ensure that the medical director can make an informed decision.

Dr. Cohn commented that the Tissue Biovigilance Subcommittee Gap Analysis Report does not describe pre-procedural agreements or review processes; it describes post-procedural reviews. The report suggested that Recommendation 3 describes inspections performed after tissues are released. Dr. Cohn indicated that inspectors would have to be empowered to perform a medical review.

Dr. Hermelin indicated that Recommendation 3 is unclear and requires revision to indicate who is accountable for the process from donor recruitment to the release of tissue products. She indicated that a responsible health care worker needs to be involved at all stages of the process to reduce variability. Dr. Hermelin and Dr. Jeng noted that blood supply facilities and facilities accredited by the EBAA do not always rely on the medical director to make donor eligibility determinations; rather, a non-physician designee may be appointed to make the determination.

The committee highlighted a recent example of an eye bank facility in New Mexico that received a warning letter issued by the FDA regarding donor eligibility determinations. This event indicated that the FDA does review donor eligibility determinations made by tissue bank medical directors.

Dr. Greenwald noted that the AATB is currently developing educational materials and databases for use by medical directors to ensure that they have the information required to make informed decisions. Barnes indicated that there is a lack of educated and experienced medical directors within the tissue industry. He noted that Recommendation 3 indicates a need for training medical directors and sharing best practices across the tissue industry. Dr. Greenwald agreed that medical directors could benefit from additional resources and that the AATB is working to develop those materials.

Recommendation 3 was revised to indicate that donor eligibility determinations made by responsible persons should be reviewed during inspections and audits to identify if non-compliance with FDA regulations had occurred. Those revisions were included to ensure that donor eligibility determinations made by responsible persons are held to a unified standard.

Dr. Basavaraju indicated that the CDC and HHS OASH, in collaboration with the National Blood Collection and Utilization Survey, perform similar actions to those described in Recommendation 4 for the blood industry. Dr. Basavaraju suggested that the CDC and HHS OASH could be the organizations responsible for implementing Recommendation 4.

Committee members noted that a lack of funding was likely the reason for not maintaining the National Tissue Collection and Utilization Survey (last performed in 2005) as a biannual survey. Therefore, they stressed that funding will be required to accomplish the tasks described in Recommendation 4.

Recommendation 4 was revised to indicate that funding be provided for the CDC and HHS OASH to collect, analyze, and publish data regarding the tissue transplantation system every 2-3 years.

Revised Recommendations and Voting

Recommendation 1:

To overcome bioburden assessment and process validation procedures that are inadequate for detecting contamination of tissue products that pose the greatest risk to recipients, microbiological process validation and surveillance programs must be risk-mitigating, standardized by experts, followed by industry, and recommended by FDA guidance. 

Dr. Cohn motioned to vote on Recommendation 1 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 2:

To improve accountability of donor eligibility determinations made by responsible persons (e.g., Medical Director, trained non-physician designees), these determinations should be reviewed during inspections (i.e., by FDA, accrediting bodies) and audits (i.e., by establishments). When noncompliance to FDA regulations is identified, they must be formally addressed. 

Dr. Cohn motioned to vote on Recommendation 2 as revised, so the recommendation was opened to a group vote. A majority of ACBTSA members voted in support of Recommendation 2, but one member (Barnes) voted against the recommendation as written.

Recommendation 3:

To inform national standards, recommendations, and policies, cell and tissue donor screening experiences, donor testing outcomes, and data regarding use of products must be funded and periodically collected, formally analyzed, and published by CDC and/or HHS OASH every 2-3 years. 

Dr. Cohn motioned to vote on Recommendation 3 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Tissue End-User/Consignee Receipt and Use Recommendations

Recommendations Originally Proposed

Recommendation 1:

To improve the capabilities and effectiveness of electronic systems that health care software companies provide for tracking tissue products, software standards-setting organizations should identify and finalize critical data elements that must be included to support tissue biovigilance, and the software must be capable of electronic exchange with EHRs. 

Recommendation 2:

To improve quality, equity, and outcomes related to tissue biovigilance, the federal agency with oversight of health care coverage should promulgate regulations that require health care facilities to use electronic documentation to track tissue products, ensure all critical data elements are documented, and require investigation of adverse events related to tissue recipient infections. 

Discussion on Tissue End-User/Consignee Receipt and Use Recommendations

Dr. Pruett described the rationale involved in developing Recommendation 1.

Dr. Josephson requested that Recommendation 1 be revised to indicate that EHR vendors must develop a biovigilance tracking system that can be integrated with EHR systems. Dr. Hermelin added that the BECS system was developed with product managers and health care workflow in mind to increase usability of the blood biovigilance system. She noted that gaps in the tissue biovigilance system include the use of multiple donor identifier and product identifier codes, inconsistent capability to maintain those codes in EHRs, and inconsistent recording of the product information (e.g., temperature). These gaps are pervasive throughout the chain of custody.

Dr. Barnhard requested clarity as to the intent of the working group. She asked whether the working group would propose subjecting EHRs or tissue establishment systems to the same regulations as medical devices, or if the working group would propose forming a new regulatory oversight system to oversee EHRs and tissue establishment systems. Dr. Pruett responded that the intent of the working group was to review existing tissue biovigilance processes and identify gaps. He noted that there are few existing regulations for EHRs that could be used to address tissue biovigilance. Dr. Pruett added that the Joint Commission, CMS, Epic, and Oracle Health were subject matter experts within the working group.

Barnes asked Dr. Pruett and Dr. Josephson whether the systems used by their health care organizations serve as the primary inventory control database for their stored tissues. Dr. Josephson noted that their health care organization has a primary inventory. Dr. Pruett described that their primary inventory control is led by three departments: their surgical operations department, their ophthalmology department, and a separate department that maintains children’s tissue. Dr. Pruett expressed interest in consolidating these tissue inventory systems but indicated that it would be a challenging task to accomplish because not all their electronic systems are harmonized.

Dr. Goodrich asked if there is anything hindering electronic software vendors from developing a system that can be used to manage tissue inventory and maintain relevant data. Dr. Pruett responded that improving tissue biovigilance is not considered cost effective and that software organizations are not financially incentivized to develop these systems. He continued to describe that the federal government should establish requirements so that software organizations and other relevant industries are incentivized to implement meaningful changes and maintain compliance with federal requirements. Several committee members agreed that the recommendations proposed by the ACBTSA should require that hospitals implement software systems with improved tissue biovigilance capabilities. These would include the capture of critical data elements identified by standards-setting organizations. Recommendation 1 was revised to include examples of standards-setting organizations.

Dr. Basavaraju asked whether CMS could require that facilities meet additional tissue biovigilance requirements to be eligible for reimbursements. Corning responded that it would take time for institutions to implement revisions to their electronic systems. She indicated that regulations that may be burdensome for organizations to implement are often given an extended timeframe for implementation while maintaining compliance. She further noted that CMS may not have the authority to require private physician offices and dental offices to use a standardized electronic system.

Several committee members expressed that it would take a substantial amount of time and money to develop a perfect software system, however, the intent of the recommendation is not to develop a perfect system. The recommendation is intended to provide an actionable goal that will improve tissue biovigilance and patient safety.

Dr. Goodrich questioned whether a funding mechanism could be encouraged within the recommendations. He described an example in which a federal agency could submit a request for proposal (RFP) describing the desired characteristics of the software system. Federal agencies could then require health care organizations to implement the developed software.

Dr. Josephson asked whether tissue banks could be responsible for developing software systems for improved tissue biovigilance rather than requiring hospitals and health care facilities to lead the development of these software systems. Recommendation 1 was revised to indicate that tissue banks should work with EHR system vendors to develop a biovigilance tracking system. Recommendation 1 was further revised to include examples of software companies.

Recommendation 1a was revised to indicate that health authorities such as HHS OASH and CMS should require the use of EHR by health care organizations. Recommendation 1a was further revised to include examples of critical data elements that should be captured by electronic software programs.

Committee members confirmed that Recommendation 1a includes a requirement to capture the final disposition of tissue products (e.g., implantation or discard). While blood centers do not currently require that the final disposition of blood products to be captured by health care facilities, recording the final disposition would enable effective tracebacks and lookbacks.

The committee elected to proceed with Recommendation 2 as revised by CMS. This version of Recommendation 2 was revised to indicate that state and federal agencies with oversight of relevant health care facilities and tissue source entities must promulgate regulations and guidance regarding documentation to ensure that tracebacks and lookbacks can be performed.

Recommendation 3 was revised to indicate that state and federal agencies with oversight of relevant health care facilities should require that adverse events be investigated and reported.

Committee members cited concerns over the potential for blood bank electronic systems and tissue bank electronic systems to intermingle. They noted that involving more people from a wider variety of backgrounds could result in reduced data quality. Further, they described concerns of cyber security and patient confidentiality.

Revised Recommendations and Voting

Recommendation 1:

To improve the capabilities and effectiveness of electronic systems that health care software companies provide for tracking tissue products, software companies (e.g., Epic, Cerner, Oracle Health) and standards-setting organizations (e.g., Office of the National Coordinator for health Information Technology certification programs, United States Core Data for Interoperability) should identify and finalize critical data elements that must be included to support tissue biovigilance.  Tissue banks should work with EHR system vendors to develop a biovigilance tracking system that can be integrated with EHR systems and ensure compliance with established biovigilance protocols. 

1. To optimize cell and tissue product traceability from donor to recipient and back to the donor, the use of electronic systems must be required by health authorities (including but not limited to HHS OASH and CMS); EHRs must have functionality to: (1) accommodate a variety of long, distinct identification codes assigned to products; and (2) manufacturers' requests for product disposition information from end-users (including human tissue that was not implanted).  

Dr. Cohn motioned to vote on Recommendation 1 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 2:

To improve quality, equity and outcomes related to tissue biovigilance, state and federal agencies with oversight of relevant health care facilities (i.e., health care clinics, physician offices, dental offices, hospitals, Critical Access Hospitals, and Ambulatory Surgical Centers) and tissue source entities (i.e., tissue procurers, processors, manufacturers, banks) must promulgate regulations and guidance that require these entities to document and track tissue products to ensure that such products can be tracked to specific end-users and tissue recipients as applicable.   

Dr. Cohn motioned to vote on Recommendation 2 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 3:

State and federal agencies with oversight of relevant health care facilities must require investigation and reporting of adverse events related to suspected or verified transmission of infectious or communicable diseases from transplanted tissue to tissue recipient(s), the tissue source entity, state and federal public health departments, the CDC, and FDA as applicable. 

Dr. Cohn motioned to vote on Recommendation 3 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Tissue Recipient Adverse Events/Reactions Recommendations

Recommendations Originally Proposed

Recommendation 1:

To improve communication from health care professionals to inform a patient who may receive a tissue product that there is a potential for risk of disease transmission, such as descriptions regarding higher risks attributed to tissue products that contain live cells, national guidelines should be developed to improve processes used to describe such risks and professional societies should be encouraged to promote those guidelines.

Recommendation 2:

Federal and state regulations should publish guidelines to assist end-users (i.e., physicians and hospitals), and physicians who treat tissue recipients, how to properly identify a reaction that may be attributed to a tissue product, and these regulators should require end-users to report tissue recipient adverse reactions and to cooperate with investigations. 

Recommendation 3:

Recipients of human tissues should give informed consent for the products they receive. Labeling information to inform clinicians of risk (e.g., absence of bioreduction) is fundamental for informed consent. 

Discussion on Tissue Recipient Adverse Events/Reactions Recommendations

Sime requested clarification as to why these recommendations suggest that physicians and hospitals act as the responsible agents.

Dr. Hermelin explained that when incompatible blood products are provided to a patient in a pre-hospital setting, the patient is provided with a wristband to identify the risks associated with the transfusion procedure. Dr. Hermelin asked whether patients that have given informed consent to receive products identified as high-risk can be assigned a label to indicate risks associated with the transplantation. Dr. Goodrich added that the recommendations should be revised to describe what should be included within a warning label and the agencies that should be involved in developing warning labels.

Recommendation 1 was revised to indicate that the CDC, federal agencies with oversight of relevant health care facilities, and professional societies should be responsible for the development of patient-centered informational materials that describe risks associated with tissue products.

Committee members acknowledged challenges associated with developing informational materials that describe risks associated with tissue products. Namely, they cite a lack of prior data collection that could be used to develop risk assessments. Further, committee members described difficulties in determining whether an adverse event is related to donor-derived infections or surgical site infections. Dr. Pruett noted that tissue banks in Europe are implementing 60-day follow-up programs to monitor adverse events. He noted that tissue banks which provide products to European countries will be required to collect this information, which can then be used to inform risk assessments in the United States.

Recommendation 1 was revised to include both informed consent and informed assent processes.

The committee decided to proceed with Recommendation 2 as edited by CMS. The recommendation was revised to indicate that state and federal agencies with oversight of relevant health care facilities must require the continuing education of applicable health care practitioners and facilities.

Recommendation 3 was revised to indicate that tissue recipients must give informed consent for the products that they receive. The recommendation was further revised to describe that labels should be developed to inform clinicians and end-users of risks associated with processed tissues and that these labels should be fundamental for patients to provide informed consent and assent.

Revised Recommendations and Voting

Recommendation 1:

To improve communication from health care professionals to inform a patient who may receive a tissue product that there is a potential for risk of disease transmission, such as descriptions regarding higher risks attributed to tissue products that contain live cells, national guidelines must be developed to improve processes used to describe such risks and professional societies must be encouraged to promote those guidelines. CDC, federal agencies with oversight of relevant health care facilities, and professional societies must also research and develop patient-centered informational materials for describing risks associated with tissue implantation (e.g., products containing live cells) as part of informed consent and assent processes. 

Dr. Cohn motioned to vote on Recommendation 1 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 2:

State and federal agencies with oversight of relevant health care facilities must publish regulations and guidance that require the continuing education of physicians, dentists, and other applicable health care practitioners and facilities who treat tissue recipients on how to properly identify and report an adverse reaction that may be attributed to a tissue product, and the duty to report and to cooperate with any subsequent investigations. 

Dr. Cohn motioned to vote on Recommendation 2 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Recommendation 3:

Recipients of human tissues must give informed consent for the products they receive. Labeling information to inform clinicians and end-users of risk (e.g., absence of bioreduction, type of treatment, preservation method) is fundamental for informed consent and assent. 

Dr. Cohn motioned to vote on Recommendation 3 as revised. The recommendation was opened to a group vote in which it received support from a majority of ACBTSA members.

Future Work

Dr. Cohn and Wilson described the future of ACBTSA activities. Dr. Cohn stated that two working groups will be convened. The first working group will address issues of reimbursement and the second will address measures that should be taken during extreme circumstances to support blood availability across the United States. These working groups should be collaborative efforts among health economists, industry representatives, and blood center representatives.

Dr. Cohn indicated that the ACBTSA had previously recommended supporting the development of a national alloantibody exchange. Work is ongoing to develop and implement a pilot exchange, including the establishment of common data elements. She indicated that the working group is developing a universal method of describing genotypes and phenotypes to increase understanding among blood centers and hospitals.

Wrap-up and Adjournment

Dr. Cohn thanked ACBTSA committee members for their efforts and willingness to donate their time and expertise to improve the tissue industry. She thanked members of HHS, OIDP, and RLA for their support during the ACBTSA meeting as well as Brubaker and Dr. Pruett for their contributions to the Tissue Biovigilance Subcommittee. Berger officially adjourned the meeting at 3:12 PM ET.

Appendix 1—List of Participants

Advisory Committee on Blood and Tissue Safety and Availability

59th Full Committee Meeting, Hybrid

Voting Members

Claudia S. Cohn, (Co-Chair), University of Minnesota

Diane Wilson, (Co-Chair), Solvita

Louis E. Barnes, American Association of Tissue Banks (AATB)

Sarah Barnhard, University of California - Davis Health

Meghan Delaney, George Washington University

Susan Galel, Stanford University

Ray Goodrich, Colorado State University

Elisa Gordon, Vanderbilt University

Jed Gorlin, Innovative Blood Resources & University of Minnesota

Daniela Hermelin, Saint Louis University School of Medicine

Bennie Jeng, University of Pennsylvania School of Medicine

Cassandra D. Josephson, Johns Hopkins All Children’s Hospital

Michelle Kameka, Florida International University

Michelle Kim, Patient Advocate

Yvette Miller, American Red Cross (ARC)                     

Paul Ness, Johns Hopkins University

Suchrita Pandey, Stanford University

Joshua Penrod, Plasma Protein Therapeutic Association (PPTA)

Stephanie Pouch, Emory University School of Medicine

Glenn Ramsey, Northwestern University Medicine

Eric Santiago-Justiniano, Fresenius Kabi

Stacy Sime, LifeServe Blood Center

Lynne Uhl, Beth Israel Deaconess Medical Center & Harvard University

Ex-officio Members

Sridhar Basavaraju, Centers for Disease Control (CDC)

Scott Brubaker, U.S. Food and Drug Administration (FDA)

Diane Corning, Centers for Medicare and Medicaid Services (CMS)

Marilyn Levi, Health Resources and Services Administration (HRSA)

David Stroncek, National Institutes of Health (NIH)

Anne Eder, U.S. Food and Drug Administration (FDA)

Presenters

Michael Bell, Centers for Disease Control and Prevention (CDC)

Melisa Greenwald, American Association of Tissue Banks (AATB)

Kristen Marshall, Colorado Department of Public Health and Environment (CDPHE)

Eoin McGrath, International Council for Commonality in Blood Banking Automation (ICCBBA)

Additional Attendees

James Berger, U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health (HHS OASH) Designated Federal Officer (DFO) for ACBTSA

Kaye Hayes, U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health (HHS OASH)

Lauren Overman, U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health (HHS OASH)

Sara Parker, U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health (HHS OASH)

Allison Petkoff, U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health (HHS OASH)

Timothy Pruett, University of Minnesota

Contractor Support

Cecelia Garcia (Science Writer), RLA

Christina Deuschle (Project Consultant), RLA

Christina Huffman (Science Writer), RLA

Mike Kavounis (Meeting Host), RLA

Meghan Walsh (Project Manager), RLA

Josh Shapiro (Meeting Planner), Capital Consulting Corporation