Spectroscopy techniques are being implemented within the biopharmaceutical industry due to their non‐destructive ability to measure multiple analytes simultaneously, however, minimal work has been applied focussing on their application at small scale. Miniature bioreactor systems are being applied across the industry for cell line development as they offer a high‐throughput solution for screening and process optimization. The application of small volume, high‐throughput, automated analyses to miniature bioreactors has the potential to significantly augment the type and quality of data from these systems and enhance alignment with large‐scale bioreactors. Here, we present an evaluation of 1. a prototype that fully integrates spectroscopy to a miniature bioreactor system (ambr®15, Sartorius Stedim Biotech) enabling automated Raman spectra acquisition, 2. In 50 L single‐use bioreactor bag (SUB) prototype with an integrated spectral window. OPLS models were developed demonstrating good accuracy for multiple analytes at both scales. Furthermore, the 50 L SUB prototype enabled on‐line monitoring without the need for sterilization of the probe prior to use and minimal light interference was observed. We also demonstrate the ability to build robust models due to induced changes that are hard and costly to perform at large scale and the potential of transferring these models across the scales. The implementation of this technology enables integration of spectroscopy at the small scale for better process understanding and generation of robust models over a large design space while facilitating model transfer throughout the scales enabling continuity throughout process development and utilization and transfer of ever‐increasing data generation from development to manufacturing.

中文翻译：

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光谱学与微型生物反应器和大规模生产生物反应器的集成——提高电流能力和模型转移

由于光谱技术能够同时测量多种分析物的非破坏性能力，因此在生物制药行业中正在实施光谱技术，然而，很少有工作专注于它们的小规模应用。微型生物反应器系统正在整个行业中应用于细胞系开发，因为它们为筛选和工艺优化提供了高通量解决方案。将小体积、高通量、自动化分析应用于微型生物反应器有可能显着增加来自这些系统的数据的类型和质量，并增强与大型生物反应器的一致性。在这里，我们对 1. 将光谱学完全集成到微型生物反应器系统（ambr®15，Sartorius Stedim Biotech) 实现自动拉曼光谱采集，2. 50 L 一次性生物反应袋 (SUB) 原型，带有集成光谱窗口。开发的 OPLS 模型证明了两种尺度下多种分析物的良好准确性。此外，50 L SUB 原型可实现在线监测，无需在使用前对探头进行消毒，并且观察到最小的光干扰。我们还展示了构建稳健模型的能力，因为在大规模上执行的诱导变化很难且成本高昂，以及跨尺度转移这些模型的潜力。