根据不同曝气孔径使用动态初始 vvm 的生物反应器放大和工艺转移新策略

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Frontiers in Bioengineering and Biotechnology Pub Date : 2024-09-10 DOI:10.3389/fbioe.2024.1461253
Huaping Ding, Huanghe Cheng, Jiaxian Wu, Fan Zhang, Can Cao, Siti Aisyah Mualif, Zhenggang Xie
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引用次数: 0

摘要

自第一个产品上市以来,单克隆抗体药物已发展成为一个市场规模超过 1000 亿美元的药物类别,这自然会产生大量的生产需求。同时,这 1000 亿美元的市场分布在 200 多种上市药物中,这表明单克隆抗体药物的生产需求是多样化的。为满足这一需求,主要供应商提供了各种规格的一次性使用生物反应器。这些规格不一的一次性生物反应器,尤其是通气孔大小的不一致,给技术转移和放大生产带来了巨大挑战,传统的恒定功率输入/容积比(P/V)和恒定每分钟容器容积(vvm)的放大策略已不能满足需要。本研究根据曝气孔径的不同,简化了生物反应器技术参数的选择。创新性地将曝气孔径与初始曝气vvm结合起来,通过正交试验法设计实验(DoE),全面研究了P/V、vvm与曝气孔径之间的关系。结果表明,在 P/V 为 20 ± 5 W/m3 的范围内,曝气孔径与初始曝气 vvm 之间存在定量关系。当曝气孔径在 1 至 0.3 毫米之间时,合适的初始曝气量为 0.01 至 0.005 立方米/分钟,这是生物反应器的最佳培养条件。初始通气量的选择与最终表达量的关系最大。后续研究在 15 升玻璃生物反应器和 500 升一次性使用生物反应器中验证了这些发现,结果与预期一致。
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A new strategy in bioreactor scale-up and process transfer using a dynamic initial vvm according to different aeration pore size
Monoclonal antibody drugs have grown into a drug category with a market size of over $100 billion since the first product was launched on the market, which naturally creates a large demand for production. At the same time, the $100 billion market is distributed among more than 200 listed drugs, which indicates that the production demand for monoclonal antibody drugs is diverse. To meet this demand, major suppliers offer single-use bioreactors of all sizes. These single-use bioreactors with different specifications, especially the inconsistency of aeration pore sizes, pose great challenges for technology transfer and scale-up production, and the conventional scale-up strategies of constant Power input/volume ratio (P/V) and constant vessel volume per minute (vvm) can no longer meet the needs. This study simplified the selection of technical parameters in bioreactors based on the differences in aeration pore size. Innovatively combined the aeration pore sizes with initial aeration vvm, and comprehensively investigated the relationship between P/V, vvm and aeration pore size by designing experiments (DoE) using the orthogonal test method. The results showed a quantitative relationship between the aeration pore size and the initial aeration vvm in the P/V range of 20 ± 5 W/m3. The appropriate initial aeration was between 0.01 and 0.005 m3/min for aeration pore size ranging from 1 to 0.3 mm, which was the optimal incubation condition in the bioreactors. The choice of initial ventilation was most related to the final expression. Follow-up studies validated these findings in a 15 L glass bioreactor and a 500 L single-use bioreactor, and the results were consistent with expectations.
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来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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