ValRun: GMP-grade Manufacturing and Quality Control of a Non-Virally engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration

VaLRun:

Raw data of "GMP-grade Manufacturing and Quality Control of a Non-Virally engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration"

(Excel-, pdf-, GraphPad-files, mp4 videos and a READ-ME text file)

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration. Instead of patient iris pigment epithelial cells, human donor tissue was used to produce the transfected cell product (“tIPE”). We implemented an extended validation of 104 tIPE productions. Procedure, operators and devices have been validated and qualified by determining cell number, viability, extracellular DNA, sterility, duration, temperature and volume. Transfected autologous cells were transplanted to rabbits verifying feasibility of the treatment. A container has been engineered to insure a safe transport from the production to the surgery site. Criteria for successful validation and qualification were based on tIPE’s Critical Quality Attributes and Process Parameters, its manufacture and release criteria. The validated process and qualified operators are essential to bring the ATMP into clinic and offer a general strategy for the transfer to other manufacture centers and personalized ATMPs.

VaLRun：《用于年龄相关性黄斑变性个性化治疗的非病毒工程化先进治疗药用产品的GMP级生产与质量控制》原始数据集
（包含Excel文件、PDF文件、GraphPad文件、MP4视频及README文本文件）

新型治疗手段的研发需对符合药品生产质量管理规范（Good Manufacturing Practice，GMP）的生产流程开展验证，并配套建立适宜的质量控制体系。对于带个性化批次的先进治疗药用产品（Advanced Therapy Medicinal Product，ATMP）而言，该验证工作极具挑战性。本团队开发了一款用于治疗年龄相关性黄斑变性的个性化细胞基因疗法，并针对该ATMP建立了GMP级生产的验证策略；受限于细胞数量稀少、批次间变异性显著且生产周期较短，该ATMP的生产与质量控制环节面临诸多难题。本研究未采用患者自体虹膜色素上皮细胞，而是利用人类供体组织制备转染细胞产物（"tIPE"）。针对104批tIPE产物，本研究开展了扩展验证工作，通过检测细胞数量、细胞活力、细胞外DNA含量、无菌性、生产时长、温度及体积等指标，完成了操作流程、操作人员与实验设备的验证与确认。研究将转染自体细胞移植至家兔体内，验证了该治疗方案的可行性。此外，本研究设计了专用转运容器，以确保从生产车间至手术场地的安全转运。验证与确认的合格标准基于tIPE的关键质量属性、工艺参数、生产流程及放行标准制定。经过验证的生产流程与经过确认的操作人员是推动该ATMP进入临床的核心要素，同时可为其他生产中心及个性化ATMP的生产转移提供通用策略。