Sheu Jonathan, Klassen Henry, Bauer Gerhard
Institute for Regenerative Cures, University of California Davis School of Medicine, Sacramento, Calif., USA.
Dev Ophthalmol. 2014;53:178-88. doi: 10.1159/000357362. Epub 2014 Apr 10.
Rapid progress has been made in the development of novel cell-based approaches for the potential treatment of retinal degenerative diseases. As a result, one must consider carefully the conditions under which these therapeutics are manufactured if they are to be used in clinical studies or, ultimately, be approved as licensed cellular therapeutics. Here, we describe the principles behind the manufacturing of clinical-grade cellular products, as well as potential methods for large-scale expansion and processing according to Good Manufacturing Practice (GMP) standards sets by the United States Food and Drug Administration. Standards for personnel, materials, procedures, and facilities required for such manufacturing processes are reviewed. We also discuss current and future scale-up methods for the manufacturing of large doses of cellular therapeutics under GMP conditions and compare the use of conventional culture methods such as tissue culture flasks and multi-layered cell factories with novel systems such as closed system hollow-fiber bioreactors. Incorporation of these novel bioreactor systems into GMP facilities may enable us to provide adequate cell numbers for multi-center clinical trials and paves the way for development of cellular therapeutics with the potential to treat very large numbers of patients.
在开发用于视网膜退行性疾病潜在治疗的新型细胞疗法方面已取得迅速进展。因此，如果这些疗法要用于临床研究，或者最终被批准为许可的细胞疗法，就必须仔细考虑其生产条件。在此，我们描述临床级细胞产品生产背后的原理，以及根据美国食品药品监督管理局制定的良好生产规范（GMP）标准进行大规模扩增和处理的潜在方法。对这种生产过程所需的人员、材料、程序和设施标准进行了审查。我们还讨论了在GMP条件下生产大剂量细胞疗法的当前和未来扩大规模方法，并比较了传统培养方法（如组织培养瓶和多层细胞工厂）与新型系统（如封闭系统中空纤维生物反应器）的使用。将这些新型生物反应器系统纳入GMP设施可能使我们能够为多中心临床试验提供足够数量的细胞，并为开发有潜力治疗大量患者的细胞疗法铺平道路。
