Richelle Anne, Corbett Brandon, Agarwal Piyush, Vernersson Anton, Trygg Johan, McCready Chris
Sartorius Corporate Research, Brussels, Belgium.
Sartorius Corporate Research, Toronto, ON, Canada.
Front Bioeng Biotechnol. 2022 Aug 22;10:948905. doi: 10.3389/fbioe.2022.948905. eCollection 2022.
There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.
生物制药行业对连续加工的兴趣日益浓厚。然而，从传统的分批工艺进行技术转移被认为是一项挑战，因为在制造规模上使用它们的协议和工具仍有待建立。在这里，我们提出了一种基于模型的方法，仅使用小规模补料分批实验中获得的知识来设计优化的中国仓鼠卵巢细胞灌注培养。所提出模型的新颖之处在于其结构的简单性。由于引入了一个新的总括变量，该变量代表细胞在培养过程中分泌的大量副产物，该模型能够在不改变其形式主义的情况下成功预测不同操作模式下的细胞行为。据我们所知，这是第一个经过实验验证的模型，能够用一组参数捕捉不同操作模式和不同规模下的培养动态。
