由于来自不同生物反应器的离子泄漏引起的mAb银基解离的差异
Xiaojing Liu1, Guohong Qin1, Jiaqi Mao1
1Department of Biology, Nanjing Chia-Tai Tianqing Pharmaceutical Co.Ltd, Fanghua Pharmaceutical Research Institute, Nanjing, 210046, China.
Pharmaceutical research
|January 22, 2026
概括
从生物反应器组件中出金属离子显著影响单克隆抗体 (mAb) 糖化的一致性. 添加化 (MnCl2) 可以解决扩大规模的问题,确保稳健的mAb生产.
科学领域:
- 生物制药制造业 生物制药制造业
- 过程开发 过程开发
- 质量属性是质量的属性.
背景情况:
- 蛋白N-糖化是单克隆抗体 (mAbs) 的关键质量属性.
- 确保mAb生产的可扩展性和批量一致性对于工艺的稳定性,安全性和有效性至关重要.
研究的目的:
- 在工艺开发过程中调查mAb银河系酶化中的规模依赖差异.
- 为了确定观察到的糖化样本变异的根本原因.
- 提出解决方案,以缓解mAb糖化中的扩大挑战.
主要方法:
- 在不同尺度 (摇瓶,2L生物反应器,200L生物反应器) 中对银河系化比进行比较分析.
- 从生物反应器材料中对金属离子浸出的研究.
- 对离子影响和缓解策略的实验验证.
主要成果:
- 在A项目中观察到银河系化的显著尺度差异,在2L生物反应器中水平更高.
- 由于2L玻璃生物反应器组件的离子液 (0.050.06μM) 导致了高基化.
- 添加0.2μM MnCl2·4H2O正常化的银河化水平,消除尺度差异.
- 对于敏感细胞系的早期糖化扩大指导,建议使用振动瓶.
- 项目B没有显示规模效应,表明细胞系对金属离子的敏感性是关键因素.
结论:
- 金属离子浸出对mAb工艺的一致性构成重大挑战.
- 包括补充在内的有针对性的解决方案可以有效地解决与设备相关的漏问题.
- 战略性地使用摇瓶可以优化工艺扩展并降低成本.
相关概念视频
Ion Channels
91.2K
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
91.2K
Common Ion Effect
46.1K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
46.1K
Precipitation of Ions
30.0K
Predicting Precipitation
The equation that describes the equilibrium between solid calcium carbonate and its solvated ions is:
The equation that describes the equilibrium between solid calcium carbonate and its solvated ions is:
30.0K
Formation of Complex Ions
25.8K
A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
25.8K
Ions and Ionic Charges
78.8K
In ordinary chemical reactions, the nucleus — which contains the protons and neutrons of each atom and thus identifies the element — remains unchanged. Electrons, however, can be added to atoms by transfer from other atoms, lost by transfer to other atoms, or shared with other atoms. The transfer and sharing of electrons among atoms govern the chemistry of the elements. During the formation of some compounds, atoms gain or lose electrons to form electrically charged particles called...
78.8K
Ions as Acids and Bases
26.2K
Salts with Acidic Ions
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
26.2K


