Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes
Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes
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DOI：
10.1002/btpr.2870
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发表时间：
2019-07-09
影响因子：
2.9
通讯作者：
Pollard, Jennifer
中科院分区：
文献类型：
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作者：
Manahan, Matthew;Nelson, Michael;Pollard, Jennifer
高通量（HTP）自动化微型生物反应器系统的最新进展显着改善了早期生物程序的开发时间表。ambr（R）250等自动化平台已证明，使用适当的缩小规模方法，能够提供从实验室到中试规模的工艺性能和产品质量的可靠估计，但与大规模商业工艺（> 10，000 L）相比的数据集有限。随着开发进入后期阶段，特别是工艺表征（PC），商业工艺的合格规模缩小模型（SDM）是生物制品许可申请（BLA）使能活动的一部分。本工作证明了ambr（R）250作为两种单克隆抗体（mAb）商业工艺（规模> 10，000 L）的代表性SDM的确认。使用适当的规模缩小方法实现了与每种mAb相关的代表性工艺性能和产品质量，并特别注意pCO（2），以确保性能和产品质量一致。在SDM的确认中使用了主成分分析（PCA）和单变量等效性检验，同时沿着工艺性能和产品质量属性的可比性统计评价。ambr（R）250可以预测这两种商业规模工艺（在中心点条件下）的细胞培养性能和产品质量。在小规模HTP系统中进行PC研究的时间节省和资源优势提高了生物制药行业更快地将产品提供给患者的潜力。
Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr (R) 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities. This work demonstrates the qualification of the ambr (R) 250 as a representative SDM for two monoclonal antibody (mAb) commercial processes at scales >10,000 L. Representative process performance and product quality associated with each mAb were achieved using appropriate scale-down approaches, and special attention was paid to pCO(2) to ensure consistent performance and product quality. Principal component analysis (PCA) and univariate equivalence testing were utilized in the qualification of the SDM, along with a statistical evaluation of process performance and product-quality attributes for comparability. The ambr (R) 250 can predict these two commercial-scale processes (at center-point condition) for cell-culture performance and product quality. The time savings and resource advantages to performing PC studies in a small-scale HTP system improves the potential for the biopharmaceutical industry to get products to patients more quickly.