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

根据 FDA 反馈，对一流的角膜冷冻保存试剂盒进行后期临床前开发和 cGMP 生产

基本信息

批准号：
10326323
负责人：
Xu Han
金额：
$ 75.4万
依托单位：
CRYOCRATE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10326323
关键词：
Address Animal Model Award Biological Assay COVID-19 pandemic Cell Count Cell Survival Cities Clinical Collaborations Contracts Cornea Cryopreservation Crystallization Data Set Development Devices Dimensions Endothelial Cells Endotoxins Engineering Evaluation Eye Banks Feedback Foundations Freezing Future Gamma Rays Goals Health Healthcare Human Ice Immunity In Vitro Industry Injections International Kansas Keratoplasty Laboratories Legal patent Letters Life Medical Device Methods Missouri Modeling Molds Optisol Oryctolagus cuniculus Osmolalities Outcome Performance Production Protocols documentation Refrigeration Research Contracts Safety Secure Small Business Innovation Research Grant Sterility Sterilization Surgeon Techniques Technology Testing Time Tissue Donors Tissues Trademark Transplantation Transplantation Surgery United States National Institutes of Health Universities Viscosity Vision Vision research Work base biomaterial compatibility cGMP production cell injury commercialization efficacy testing improved in vivo evaluation mechanical device meetings new technology novel operation pre-clinical preclinical development prevent prospective safety testing

项目摘要

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.

概括 NIH SBIR和Coulter Foundation奖的先前支持允许冷冻团队开发一部小说 Corneal Cryoprestration Technology，并具有国际专利保护，并被称为Icyeye®。 iCyeye®是一个包括有效的冷冻保存介质C80EZ®的套件，可防止存储期间的冰重结晶大约-80oC和一种新型的机械装置，可以物理地将细胞破坏冰晶与组织分离在冷冻期间。结合两种作用机制，该套件独特地实现了长期（至少6个月）通过冷冻保存在常规-80°C的冰柜中储存角膜，并具有透视后的内皮细胞活力和组织质量毫不留情地满足并超过了移植的临床标准。临床用途这项新型技术不仅将提高组织质量的移植和眼库的效率一般的操作，但也将允许眼库在任何以后的医疗保健期间保持正常运作危机类似于当前的Covid-19大流行。 510年前（K）与FDA进行了潜在提交的会议。基于FDA反馈 ICYEYE®技术以获得相关的许可，在这个项目中，我们与我们的合作组织法规顾问（Cardinal Health），合同制造组织（Bryllan和Plas-Tech），合同研究组织（Catealent），学术联赛（密苏里大学 - 堪萨斯城市视觉研究中心）和三个当地的眼库合作伙伴，以实现以下里程碑： I.Icyeye®套件的生产符合510（k）提交所需的GMP资格； ii。生物相容性评估表明符合FDA指南以及体外和体内使用标准动物模型评估安全性和效率等同于现有的制冷协议；和 iii。使用人角膜对安全性和效率的体外评估证明了Icyeye®技术等同于现有的制冷协议。根据这些资格，我们将完成基于生产线的510（k）提交和最终确定在项目结束之前，进一步的FDA反馈。我们预计iCyeye®大量临床使用 FDA清除后三年内技术，为该行业提供了改善的供体组织质量和国内外使用的运营效率更高。