改进下游流程相关的可制造性基于蛋白质工程-一个可行性研究
Florian Capito1, Ting Hin Wong1,2, Christine Faust3
1Sanofi-Aventis Deutschland GmbH, CMC Microbial Platform Downstream Process Development Industriepark Höchst Frankfurt am Main Germany.
Engineering in life sciences
|September 5, 2024
概括
通过调整生物治疗蛋白质的表面电荷,可以通过高效的净化来提高制造能力. 这一策略有助于去除宿主细胞蛋白 (HCP) 和病毒,降低制造成本.
科学领域:
- 生物制药制造业 生物制药制造业
- 蛋白质工程是指蛋白质的工程.
- 下游加工 下游加工
背景情况:
- 生物治疗药物的可制造性至关重要,它超越药物稳定性,包括净化效率.
- 目前的文献往往忽视了下游工艺相关的可制造性,而是专注于配方.
- 有效地去除与过程相关的杂质,如宿主细胞蛋白 (HCP) 和病毒,对于患者的安全至关重要.
研究的目的:
- 研究修改生物治疗性蛋白质表面电荷的潜力,以提高下游净化.
- 通过表面电荷适应来提高可制造性的概念证明.
主要方法:
- 产生一种具有改变表面电荷特征的GLP1-受体-激动剂-Fc-域-FGF21融合蛋白的工程变体.
- 使用离子交换染色学 (AEX) 评估净化效率.
主要成果:
- 证明改变聚变蛋白的表面电荷分布可以实现高效的净化.
- 展示了在高pH值下运行离子交换色谱的可行性,最大限度地提高了产品回收率.
- 在净化过程中成功去除宿主细胞蛋白 (HCP) 和病毒.
结论:
- 调整生物治疗蛋白质的表面电荷是改善可制造性的可行策略.
- 这种方法有助于有效地去除关键杂质,如HCP和病毒.
- 优化表面电荷可以导致更具成本效益的生物制药制造工艺.
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