Integrated design of H2O2 decontamination processes and scheduling in sterile drug product manufacturing
Integrated design of H2O2 decontamination processes and scheduling in sterile drug product manufacturing
复制标题
无菌药品生产中 H2O2 净化工艺和调度的集成设计
DOI：
10.1007/s12247-020-09434-4
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发表时间：
2020
影响因子：
2.6
通讯作者：
Sugiyama Hirokazu
中科院分区：
文献类型：
--
作者：
Yabuta Keisho;Futamura Haruka;Kawasaki Koji;Sugiyama Hirokazu
PurposeWe探讨了一体化设计的H2 O2去污过程和调度在无菌药物产品制造，考虑生产率和产品quality.MethodsModels开发，（i）处理的灌装和多个批次/产品的转换调度和（ii）配置的水H2 O2注入率到隔离器作为一个过程参数。所有计划的批次和产品的无菌保证水平的总生产时间被定义为生产力和产品quality的目标函数，respectively. ResultsThemodels被应用到15批（不同的产品和批量大小）的生产中的去污和调度选项的多目标评价。帕累托最优的解决方案，表明这两个目标之间的权衡。帕累托前沿的倾斜度增加时，产品变得更容易残留的H2 O2曝气后，当批量变得smaller.ConclusionThe定量结果证实了增加的影响的配置的去污过程中的生产力和产品质量。H2 O2敏感产品的小批量生产越来越受欢迎，特别是对于生物制药，本研究的结果鼓励在无菌药品生产中协同开发去污工艺和生产计划。
PurposeWe explored the integrated design of H2O2decontamination processes and scheduling in sterile drug product manufacturing, considering productivity and product quality.MethodsModels were developed that (i) deal with the scheduling of filling and the changeover of multiple batches/products and (ii) configure the aqueous H2O2injection rate into the isolator as a process parameter. The total production time for all planned batches and the sterility assurance level of the products were defined as the objective functions for productivity and product quality, respectively.ResultsThe models were applied to a multiobjective evaluation of the decontamination and scheduling options in the production of 15 batches (different products and batch sizes). Pareto-optimal solutions were obtained that indicated a trade-off between the two objectives. The inclination of the Pareto frontier increased when the product became more vulnerable to residual H2O2after aeration and when the batch size became smaller.ConclusionThe quantitative results confirmed an increased impact of the configuration of the decontamination process on both productivity and product quality. The small batch-size production of H2O2-sensitive products is increasingly popular, especially for biopharmaceuticals, and the results of this study encourage the collaborative development of decontamination processes and production schedules in sterile drug product manufacturing.