Bioreactor Process Parameter Screening Utilizing a Plackett-Burman Design for a Model Monoclonal Antibody
Bioreactor Process Parameter Screening Utilizing a Plackett-Burman Design for a Model Monoclonal Antibody
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DOI：
10.1002/jps.24420
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发表时间：
2015-06-01
影响因子：
3.8
通讯作者：
Read, Erik K.
中科院分区：
文献类型：
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作者：
Agarabi, Cyrus D.;Schiel, John E.;Read, Erik K.
一致的高质量抗体产量是细胞培养生物处理的关键目标。这个终点通常在商业环境中通过开发过程中生物反应器参数的产品和工艺工程来实现。当工艺复杂且未优化时，成分和控制的微小变化可能会产生不理想的成品质量。因此，对目前已验证的工艺提出的变更通常需要证明，并报告给美国FDA批准。最近，基于实验设计的方法已经被探索，通过更好地理解影响产品关键质量属性的产品和过程变量，快速有效地实现优化产量的目标。在这里，我们提出了一个实验室规模的模型培养，我们将Plackett-Burman筛选设计应用于平行培养，以研究11个过程变量的主要影响。这个练习使我们能够确定这些变量的相对重要性，并确定最重要的因素，以进一步优化，以控制理想和不理想的聚糖谱。我们发现，与培养温度和非必需氨基酸补充相关的工程变化显著影响了与聚焦化、-半乳糖基化和唾液化相关的聚糖分布。这些都对单克隆抗体产品的质量至关重要。(3)中国医药科学，2015,(4):391 - 398
Consistent high-quality antibody yield is a key goal for cell culture bioprocessing. This endpoint is typically achieved in commercial settings through product and process engineering of bioreactor parameters during development. When the process is complex and not optimized, small changes in composition and control may yield a finished product of less desirable quality. Therefore, changes proposed to currently validated processes usually require justification and are reported to the US FDA for approval. Recently, design-of-experiments-based approaches have been explored to rapidly and efficiently achieve this goal of optimized yield with a better understanding of product and process variables that affect a product's critical quality attributes. Here, we present a laboratory-scale model culture where we apply a Plackett-Burman screening design to parallel cultures to study the main effects of 11 process variables. This exercise allowed us to determine the relative importance of these variables and identify the most important factors to be further optimized in order to control both desirable and undesirable glycan profiles. We found engineering changes relating to culture temperature and nonessential amino acid supplementation significantly impacted glycan profiles associated with fucosylation, -galactosylation, and sialylation. All of these are important for monoclonal antibody product quality. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1919-1928, 2015