FDA EID Workshop: Day 2 Organs, Tissues and Cells Melissa A. Greenwald, MD Blood Products Advisory Committee 26 July 2010 Gaithersburg, MD

The EID Workshop—Day Two AttendeesOverview –Presentations –2 panel discussions Review of major discussion points

Transplantation Community Stakeholders Present “Conventional” Tissues Cell Therapy Products Ocular Tissues Reproductive Tissues Organs –Transplant Infectious Disease –Organ Procurement and Transplantation Network/UNOS Disease Transmission Advisory Committee Blood Products

Why did we have the meeting? There are always “new” diseases that are potentially transplant-transmissible –Trypanosoma cruzi –West Nile Virus –Dengue Not feasible to screen and test for everything Need for a coordinated process to prioritize and scientifically evaluate pathogens of concern Public dialogue with major stakeholders to develop a path forward

Science to Inform Policy FDA is responsible for determining screening and testing policy for donors of human cells, tissues and cellular and tissue-based products (HCT/Ps) FDA does not regulate Solid Organ Transplantation (SOT) or organ donor screening and testing policy; however –Shared donors –Regulate infectious disease tests Application of scientific information obtained may be different between cells/tissues and SOT, but we have need for the same basic information, and ultimately the same goal—recipient safety

Overview The ultimate goal is patient safety. Views of the best approach to safety vary based on factors such as urgency for transplantation (life-saving transplants), transmission (infectious risk), cost (deployment of molecular testing), and research agenda (funding agencies). These viewpoints must coalesce into a coherent program. Significant resources need to be deployed to develop a research agenda that will address gaps in donor screening paradigms and to assess the risks inherent to transplantation.

Overview The incidence of transmission associated with allografts is thought to be low, historically There are few data that directly assess the risk of transmission of potential pathogens by tissues or organs Policy decisions must be made using the best available information in the effort to improve transplantation outcomes If specific data are unavailable, resultant donor screening and testing policies tend to be conservative—erring on the side of caution

Overview The cell, ocular, tissue and organ communities are charged with evaluating the infectious disease risks of transplantation Collaboration will be key in advancing transplantation infectious disease transmission research

Session One Focused on surveillance approaches for assessing infectious disease transmission in cell, tissue, and organ recipients Surveillance for infectious disease transmission is important in assessing safety of cell, tissue and organ products Limitations to surveillance –Under-reporting is common –Current systems could be improved notably in communication of data between stakeholders, public health authorities, regulatory authorities, physicians –Surveillance alone is unable to detect all ID transmission – current testing might be expanded

Key Points: Session One To enhance surveillance efforts, need to address –donor identifiers –standardized nomenclature and definitions –tracking –denominator data –communication

Key Points: Session One Important to improve surveillance of –Transplant recipients –Emerging diseases (both common and unusual) Need to strike the right balance between safety and availability

Session Two Reviewed infectious disease transmission events to date for clues to use in identifying future pathogens of concern Discussed information needed to formally evaluate infectious disease transmission risks Panel discussion explored gaps in data that are needed to best assess infectious transmission risk

Key Points: Session Two Infectious disease transmissions via organs, cells and tissues occur, but are incompletely assessed Risk assessment modeling can be a useful tool to identify data gaps and estimate transmission risks, but such risk estimates are only as good as the scientific theory and data going into the model

Key Points: Session Two Key research needs: –Seroprevalence data (estimates vs. measured) –Denominator data –Transmissibility data –Validate donor history questioning and use of standardized questionnaire –Donor testing –Sterilization and pathogen reduction –New approaches to transmission studies

Session Three Focused on research issues –Relevant research currently performed –Challenges in performing research –Overall research gaps Funding Research and surveillance needs are cross cutting among the cell, tissue and organ communities, collaboration will be a key to successful implementation

Key Points: Session Three Donor derived infectious disease transmissions are infrequent events and are difficult to measure Transmission rates may be variable across donors (ethnicity, geography), and between organ, cells, and various tissues Need protocols and collaboration to collect donor and recipient data (e.g., donor information, results of donor screening and testing, processing methods, surveillance)

Key Points: Session Three Tissue handling and processing affect transmissibility, but are difficult to quantify because processing methods are inconsistent, proprietary, and there is scant published information Need for commitment to open communication and cooperative data collection

Thank You! Questions?