Late-stage Preclinical Development and cGMP Production of a First-in-Class Cornea Cryopreservation Kit Based on FDA Feedback

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SUMMARY Previous support from NIH SBIR and Coulter Foundation awards allowed the CryoCrate team to develop a novel corneal cryopreservation technology, trademarked as IcyEye®, with international patent protection. IcyEye® is a kit that includes an efficient cryopreservation medium, C80EZ®, that prevents ice recrystallization during storage at approx. -80oC and a novel mechanical device that physically separates cell damaging ice crystals from tissues during freezing. Combining both mechanisms of action, this kit uniquely enables long-term (at least 6 months) storage of corneas through cryopreservation in regular -80°C freezers with post-thaw endothelial cell viability and tissue quality unprecedently meeting and exceeding clinical criteria for transplantation. The clinical use of this novel technology will not only improve tissue quality for transplantation and the efficiency of eye bank operations in general, but will also allow eye banks to maintain normal operations during any future health care crises similar to the current COVID-19 pandemic. A pre-510(k) meeting with the FDA for the potential submission took place recently. Based on FDA feedback for the IcyEye® technology to gain the associated clearances, in this project we organized the collaboration with our regulatory consultant (Cardinal Health), contract manufacturing organizations (Bryllan and Plas-tech), contract research organization (Catalent), academic co-inventor (University of Missouri – Kansas City Vision Research Center), and three local eye bank partners, to achieve the following milestones: I. The production of IcyEye® kits meets GMP qualifications required for 510(k) submission; II. The biocompatibility assessment shows compliance with FDA guidance and the in vitro and in vivo evaluation of safety and efficacy using a standard animal model demonstrates IcyEye® technology to be equivalent to existing refrigeration protocols; and III. The in vitro evaluation of safety and efficacy using human corneas demonstrates IcyEye® technology to be equivalent to existing refrigeration protocols. Based on those qualifications, we will complete the 510(k) submission and finalize of the production line based on further FDA feedback before the end of the project period. We expect extensive clinical use of the IcyEye® technology within three years after FDA clearance, providing the industry with improved donor tissue quality and higher operational efficacy for both domestic and international use.