Abstract 18 Leveraging the BMDI Cord Blood Bank to Create a GMP-Compliant Cord Blood (CB)–Derived Induced Pluripotent Stem Cell (iPSC) Master Cell Bank (MCB) for Potential Allogeneic Therapies

Introduction The BMDI Cord Blood Bank (CBB) in Melbourne is a public cord blood bank that operates under a Good Manufacturing Practice (GMP) cell-manufacturing licence from the Therapeutic Goods Administration (TGA) and is internationally accredited by the Foundation for the Accreditation of Cellular Therapy (FACT). An iPSC MCB derived from cord blood (CB) could form the basis of future cell-based therapies. Banked CB is an ideal source of starting material for the creation of iPSCs, with a host of advantages not afforded by other cell sources. Objectives We have previously described the technical aspects of creating “GMP-like” iPSCs from banked CB (https://www.frontiersin.org/articles/10.3389/fcell.2022.835321/full). Our objective is to leverage the CBB to transition our “GMP-like” protocols, developed in the research lab, into a fully GMP-compliant environment. Methods A small lab within the CBB was seconded for the purpose of establishing an Institutional Biosafety Committee (IBC) – approved PC2 laboratory to create GMP-compliant iPSC lines from banked cord blood. CB donors have been re-consented to use a portion of their banked HLA homozygous CB to create iPSC lines (https://doi.org/10.1093/stcltm/szac060). The CBB Quality Framework was replicated as a side module, mimicking all key components. Results * Established an IBC-approved PC2 laboratory within the GMP-compliant CBB facility. * Developed a Quality Systems framework in-line with the FACT Common Standards for Cellular Therapy, leveraging off that in place for the CBB. * Tested and validated the process in its entirety, including robustness of the Quality Systems, by the creation of new CB-derived “GMP-mock” iPSC lines. * Established collaborations for pre-clinical studies to use our CB-derived iPSC lines for therapies directed towards retinal and neurological repair, NK and CAR-NK immunotherapies. Discussion A PC2 GMP-compliant laboratory has been established. Challenges, and solutions, will be discussed. Quality systems have been developed that mimic those in place for the CBB. The robustness of the Quality framework and GMP manufacturing have been confirmed by a full mock-run to create new CB-derived iPSC lines. Lower grade reagents used for the mock-run have now been swapped out for more expensive, fully GMP-certified (CTS) reagents and creation of our first fully GMP CB-derived iPSC line is underway.