NCATS-DPI-22-0101 - CREATION OF AN OPEN-SOURCE PROCESS TO MANUFACTURE AAV VECTOR-BASED GENE THERAPY CANDIDATES FOR NON-COMMERCIAL CLINICAL STUDIES

项目目标： ·制定一种开放获取程序，以产生目前广泛使用的至少两种AAV血清型。所有AAV血清型都将使用GFP基因和NCATS确定的感兴趣基因(GOI)来验证实验室规模的过程。 ·通过制造适用于所有AAV血清型(非GMP)的NCATS GOI，在50 L中试规模和随后在200 L生物反应器规模上生产，展示了这一过程的可扩展性。 ·为在整个开发阶段生成的材料的过程中测试和质量属性制定所有必要的分析方法，以支持监管备案。 ·提供全面的项目管理支持 ·在流程开发和最终流程定义阶段提供质量审核支持 ·为研究新药(IND)申请的化学、制造和控制(CMC)部分的准备提供监管支持 ·在cGMP制造临床使用的AAV-GOI材料，并验证用于释放和稳定性分析的相关分析方法。 ·对药物物质和药物产品进行长达48个月的稳定性研究 ·为细胞库、药物物质和药物产品的储存和运输提供库存支持

Project Objectives: • Develop an open- access process for the generation of at least two of the AAV serotypes broadly in current use. All AAV serotypes will use a GFP gene, and a gene of interest (GOI) identified by NCATS to validate the lab scale process. • Demonstrate the scalability of that process by manufacturing the NCATS GOI for all AAV serotypes (non-GMP) at 50 L pilot scale and subsequently at a 200 L bioreactor scale. • Develop all the required analytical methods for in-process testing and quality attributes of the material generated throughout the development stages to support regulatory filings. • Provide comprehensive project management support • Provide quality audit support during the process development and final process definition stage • Provide regulatory support for preparation of the Chemistry, Manufacturing and Controls (CMC) section of an Investigational New Drug (IND) application • Manufacture AAV-GOI material at cGMP for clinical use and validate relevant analytical methods for release and stability analysis. • Perform stability studies on the drug substance and drug product for up to 48 months • Provide inventory support for storage and shipping of cell banks, drug substance and drug product