Process economics evaluation and optimization of adeno-associated virus downstream processing.
Process economics evaluation and optimization of adeno-associated virus downstream processing.
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腺相关病毒下游加工的工艺经济学评估和优化。
DOI：
10.1002/bit.28402
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发表时间：
2023
影响因子：
3.8
通讯作者：
Lyle A
中科院分区：
文献类型：
--
作者：
Lyle A
腺相关病毒（AAV）的生产传统上集中在实验室规模的技术来培养和纯化载体产品，导致生产能力的限制。本文提出的工具评估了在高AAV需求下使用不可扩展技术的可行性，并确定了满足成本和纯度目标的大规模最佳流程图。该决策工具包括（a）详细的工艺经济学模型，包括AAV上游和下游技术的相关质量平衡、规模和成本计算公式，（B）内置蒙特卡罗模拟，用于评估不确定性，以及（c）强力优化算法，用于快速调查最佳纯化组合。结果总体上突出表明，转向更可扩展的上游和下游加工替代品在经济上是有利的。基础案例分析显示了利用悬浮细胞培养物优于贴壁培养物的成本和稳健性优势，以及全色谱纯化平台优于分批超滤。扩展可用的纯化选项集，深入了解满足成本和纯度目标的最佳组合。随着纯度目标的增加，最佳精制溶液从非衣壳纯化多模式色谱转移到阴离子交换色谱或连续超离心。
Adeno‐associated virus (AAV) manufacturing has traditionally focused upon lab‐scale techniques to culture and purify vector products, leading to limitations in production capacity. The tool presented in this paper assesses the feasibility of using non‐scalable technologies at high AAV demands and identifies optimal flowsheets at large‐scale that meet both cost and purity targets. The decisional tool comprises (a) a detailed process economics model with the relevant mass balance, sizing, and costing equations for AAV upstream and downstream technologies, (b) a built‐in Monte Carlo simulation to assess uncertainties, and (c) a brute‐force optimization algorithm for rapid investigation into the optimal purification combinations. The results overall highlighted that switching to more scalable upstream and downstream processing alternatives is economically advantageous. The base case analysis showed the cost and robustness advantages of utilizing suspension cell culture over adherent, as well as a fully chromatographic purification platform over batch ultracentrifugation. Expanding the set of purification options available gave insights into the optimal combination to satisfy both cost and purity targets. As the purity target increased, the optimal polishing solution moved from the non‐capsid purifying multimodal chromatography to anion‐exchange chromatography or continuous ultracentrifugation.
97. 使用连续流超速离心大规模纯化 AAV
DOI：
--
发表时间：
2016
期刊：
影响因子：
--
作者：
Haifeng Chen;Sandra Marino;Ching Yi Ho
通讯作者：
Ching Yi Ho
改进空间：解决病毒载体下游工艺单元操作欠佳的问题
DOI：
--
发表时间：
2019
期刊：
Cell and Gene Therapy Insights
影响因子：
--
作者：
C. Glover;Daniel Smith;D. Marshall
通讯作者：
D. Marshall
用于人类基因治疗的腺相关病毒载体的质量控制测试、表征和关键质量属性
影响因子：
4.7
作者：
J. F. Wright
通讯作者：
J. F. Wright