Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland.
Manufacturing Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland.
Cells. 2022 Mar 17;11(6):1016. doi: 10.3390/cells11061016.
Cultured autologous human articular chondrocyte (HAC) implantation has been extensively investigated for safe and effective promotion of structural and functional restoration of knee cartilage lesions. HAC-based cytotherapeutic products for clinical use must be manufactured under an appropriate quality assurance system and follow good manufacturing practices (GMP). A prospective clinical trial is ongoing in the Lausanne University Hospital, where the HAC manufacturing processes have been implemented internally. Following laboratory development and in-house GMP transposition of HAC cell therapy manufacturing, a total of 47 patients have been treated to date. The main aim of the present study was to retrospectively analyze the available manufacturing records of the produced HAC-based cytotherapeutic products, outlining the inter-individual variability existing among the 47 patients regarding standardized transplant product preparation. These data were used to ameliorate and to ensure the continued high quality of cytotherapeutic care in view of further clinical investigations, based on the synthetic analyses of existing GMP records. Therefore, a renewed risk analysis-based process definition was performed, with specific focus set on process parameters, controls, targets, and acceptance criteria. Overall, high importance of the interdisciplinary collaboration and of the manufacturing process robustness was underlined, considering the high variability (i.e., quantitative, functional) existing between the treated patients and between the derived primary HAC cell types.
异体培养的人关节软骨细胞（HAC）植入已被广泛研究，以安全有效地促进膝关节软骨损伤的结构和功能恢复。用于临床的基于 HAC 的细胞治疗产品必须在适当的质量保证体系下制造，并遵循良好生产规范（GMP）。洛桑大学医院正在进行一项前瞻性临床试验，该医院已内部实施了 HAC 制造工艺。在 HAC 细胞治疗制造的实验室开发和内部 GMP 转化之后，迄今为止已治疗了 47 名患者。本研究的主要目的是回顾性分析已生产的基于 HAC 的细胞治疗产品的可用制造记录，概述 47 名患者在标准化移植产品制备方面存在的个体间变异性。这些数据用于改进和确保细胞治疗护理的持续高质量，以便进一步进行临床研究，这是基于对现有 GMP 记录的综合分析。因此，进行了基于重新风险分析的过程定义，特别关注过程参数、控制、目标和验收标准。总的来说，考虑到治疗患者之间以及衍生的原代 HAC 细胞类型之间存在的高度变异性（即定量、功能），强调了跨学科合作和制造过程稳健性的高度重要性。
