Director, Analytical and Therapeutic Development Gameto Inc., United States
Abstract: In vitro maturation (IVM) is a fertility treatment that enables oocyte maturation outside of the body, greatly reducing the need for the high hormone doses typically required to retrieve fertilization-ready oocytes. We have recently demonstrated that supplementation of IVM media with hiPSC-derived ovarian support cells (OSCs) significantly improves oocyte maturation and euploid embryo formation by replicating the complex ovarian environment in vitro. To develop an off-the-shelf therapy capable of meeting the growing demand for assisted reproductive technologies, currently increasing 5-10% worldwide annually, manufacturing capacity must scale up to accommodate that need. In preparation for clinical and commercial manufacturing of this off-the-shelf ex vivo cell therapy, we scaled up OSC production to achieve up to 10,000 vials per lot. This scaling effort involved addressing key challenges, including high-throughput fill-and-finish processes, formulation optimization, and comprehensive lot release strategies to maintain cell therapy standards and ensure product quality across the entire lot. These strategies were designed to maintain the integrity of critical quality attributes such as identity, conformance, potency, and safety. We have demonstrated that our process can accommodate batch sizes from 1,000 to 10,000 doses, ensuring consistent quality across the lots. Our findings support the adoption of similar strategies for high-throughput manufacturing of hiPSC-derived products. Furthermore, this work represents the first description of a large scale hiPSC-derived therapy aimed at enhancing IVF outcomes and advancing women’s health, paving the way for broader clinical applications.
