Sepsis Screening for Tissue Donation
Two recent Mycobacterium tuberculosis outbreaks linked to bone allografts led to FDA’s inspectional focus on proper donor screening and practices by eye and tissue banks regarding to sepsis.
FDA released Important Information for Human Cell, Tissue and Cellular and Tissue-based Product (HCT/P) Establishments Regarding Tuberculosis Outbreaks Linked to a Bone Matrix Product on September 6, 2023. This alert outlined risk mitigation strategies to identify risk factors, conditions, clinical evidence, and physical evidence that can be associated with an increased risk for TB (including active TB and LTBI) and/or an increased risk of sepsis.
Several FDA inspections of eye banks have resulted in Form FDA 483, Inspectional Observations, for not determining donors to be ineligible with a diagnosis of sepsis. All cited eye banks utilized the same Infectious Disease consultant and in some cases had only been reviewing records from a donor’s last 5 days in the hospital.
EBAA has been monitoring the situation and met with the Center for Biologics Evaluation and Research (CBER) Office of the Center Director, Super Office of Therapeutic Products, Office of Compliance and Biologics Quality, and Office of Communication, Outreach and Development in a virtual EBAA/FDA Executive Liaison Meeting on April 18, 2024, to discuss how eye banks evaluate donors with a differential diagnosis of sepsis.
We discussed the use of Infectious Disease consultants to review the medical records to provide an expert opinion. We also shared our concerns about discordant HBsAg test results and the 2023 increase in ocular tissue not released due to HBsAg test results.
The Medical Advisory Board (MAB) discussed the recent FDA inspectional focus on donor eligibility with regard to sepsis following the release of our May 17, 2024 Regulatory Alert and formed a Sepsis Working Group to study the issue more closely.
EBAA requested information from eye banks to better understand the data related to sepsis concerns.
41 eye banks responded to our sepsis data requests for 2023, which accounts for 75.9% of the domestic transplants for that year.
Total number of referrals deferred due to sepsis concerns: – 51,843
Total number of donors recovered with sepsis concerns. – 7,587
Total number of donors with sepsis concerns who were determined eligible and were transplanted. – 3,906
Additionally, the Medical Review Subcommittee (MRS) reviewed all 2023 infectious adverse reaction reports in OARRS (16 endophthalmitis and 13 keratitis cases). The MRS was asked to review the appropriateness of accepting the donor, whether the donor was septic prior to recovery, and the likelihood that sepsis was related to the recipient infection.
All but one donor was accepted consistent with existing protocols and FDA regulations. This donor had clinical evidence and a diagnosis of sepsis a few hours before death and should have been determined to be ineligible. One donor had pneumonia and another had UTI as a source of infection, but did not fulfill the criteria for SIRS and consequently sepsis.
There was consensus that further education was needed to help eye banks comply with the current sepsis regulations and a best practices paper is in the works. However, there was no evidence to suggest that SIRS transmitted infection to the recipient, as there was no match in cultures between donor and recipient, including the septic donor associated with an ocular infectious adverse event.
Additional guidance from FDA may be forthcoming and EBAA is actively working to support our members through this process. CBER’s Guidance Agenda for CY 2024 includes two new final guidance documents on reducing the risk of Mycobacterium tuberculosis transmission through HCT/Ps and transmission of disease agents associated with sepsis for HCT/P donors, in addition to the long-awaited Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Draft Guidance for Industry.
