根据ICH Q14生命周期原则,对治疗性抗体的传统N-甘氨酸分析方法的稳定性评估
Ming-Ching Hsieh1, Chao Richard Li2, Margaret A Velardo3
1Analytical Sciences, Eli Lilly and the Company, Branchburg, NJ 08876, USA.
Antibodies (Basel, Switzerland)
|January 21, 2026
概括
传统的N-glycan分析方法需要谨慎管理. -N-糖化酶F (PNGase F) 酶来源,SPE卡片和试剂稳定性的变化可能会影响治疗抗体糖化分析的稳定性.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 对于治疗性抗体而言,N-甘氨酸的分析是至关重要的,它会影响其功能和药理动力学.
- 确保传统分析方法的稳定性对于持续的药物质量至关重要.
研究的目的:
- 为治疗性抗体MAB1.1.重新评估传统的N-甘氨酸分析方法.
- 评估不同-N-糖酶F (PNGase F) 酶来源,固相提取 (SPE) 盒和试剂稳定性对方法稳定性的影响.
- 确保分析性能与国际协调理事会 (ICH) Q14生命周期管理原则保持一致.
主要方法:
- 采用了传统的N-糖甘分析方法,包括2-氨基酸 (2-AA) 标记和正常相高性能液体染色学 (HPLC).
- 评估了各种商业PNGase F酶来源的性能.
- 测试了多种SPE弹格式的糖甘回收和可变性.
- 评估了2-AA标记试剂随时间的稳定性.
主要成果:
- 在不同的商业PNGase F酶来源中观察到显著的性能差异.
- 某些SPE弹药盒表现出不良的恢复和高的变化,特别是对于化甘氨酸.
- 2-AA标记试剂在几天内迅速降解,影响了测试可靠性.
结论:
- 该研究强调了对风险控制和分析方法生命周期管理的持续改进的关键需求.
- 确保遗留的糖基化分析方法的稳定性对于保持治疗性抗体的质量和一致性至关重要.
- 实施生命周期管理原则 (ICH Q14) 对于持续的分析方法可靠性至关重要.
相关概念视频
01:22Lifecycle of Erythrocytes
4.7K
Erythrocytes, also known as red blood cells, constantly move through blood capillaries. As a result, they damage their plasma membrane due to the continuous friction. Typically, after 100 to 120 days, erythrocytes become rigid and fragile as they wear out. As they pass through small vessels in the spleen and liver, they can get trapped and break apart into fragments.
The resident phagocytic macrophages deal with these damaged cells by engulfing them and separating their globin and heme groups....
The resident phagocytic macrophages deal with these damaged cells by engulfing them and separating their globin and heme groups....
4.7K
04:08The Uncertainty Principle
31.4K
Werner Heisenberg considered the limits of how accurately one can measure properties of an electron or other microscopic particles. He determined that there is a fundamental limit to how accurately one can measure both a particle’s position and its momentum simultaneously. The more accurate the measurement of the momentum of a particle is known, the less accurate the position at that time is known and vice versa. This is what is now called the Heisenberg uncertainty principle. He...
31.4K
01:49Hardy-Weinberg Principle
76.0K
Diploid organisms have two alleles of each gene, one from each parent, in their somatic cells. Therefore, each individual contributes two alleles to the gene pool of the population. The gene pool of a population is the sum of every allele of all genes within that population and has some degree of variation. Genetic variation is typically expressed as a relative frequency, which is the percentage of the total population that has a given allele, genotype or phenotype.
76.0K
03:06The Pauli Exclusion Principle
59.0K
The arrangement of electrons in the orbitals of an atom is called its electron configuration. We describe an electron configuration with a symbol that contains three pieces of information:
59.0K
03:02The Aufbau Principle and Hund's Rule
72.3K
To determine the electron configuration for any particular atom, we can build the structures in the order of atomic numbers. Beginning with hydrogen, and continuing across the periods of the periodic table, we add one proton at a time to the nucleus and one electron to the proper subshell until we have described the electron configurations of all the elements. This procedure is called the aufbau principle, from the German word aufbau (“to build up”). Each added electron occupies the...
72.3K
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
183
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
183