Scale‐dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies

浸出(土壤学) 糖基化 单克隆抗体 化学 抗体 生物反应器 生物化学 生物 免疫学 有机化学 生态学 土壤水分
作者
Jenna Williamson,Jennifer Miller,Joseph McLaughlin,Rodney G. Combs,Chia Chu
出处
期刊:Biotechnology Progress [Wiley]
卷期号:34 (5): 1290-1297 被引量:11
标识
DOI:10.1002/btpr.2662
摘要

N ‐linked glycosylation profiles are routinely characterized on mammalian‐derived protein therapeutic products and achieving consistency in the product‐associated glycan attributes is an important indicator that the manufacturing process is under control. More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy. During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2‐L, 100‐L, and 6,000‐L scales were observed. Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time. Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike‐in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles. Surprisingly, the 2‐L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation. The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors. The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control. © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 34:1290–1297, 2018
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Akim应助菠菜采纳,获得100
刚刚
华仔应助丰富的小白菜采纳,获得10
1秒前
4秒前
5秒前
科目三应助Dudu采纳,获得30
6秒前
仁爱听露完成签到 ,获得积分10
6秒前
7秒前
10秒前
杨杨完成签到 ,获得积分10
10秒前
YY发布了新的文献求助10
11秒前
xuanyu应助费费采纳,获得30
11秒前
英俊的铭应助淡定小白菜采纳,获得10
11秒前
玉玉发布了新的文献求助10
12秒前
青椒超人关注了科研通微信公众号
12秒前
小殷发布了新的文献求助10
14秒前
刘星宇完成签到,获得积分10
16秒前
倩倩完成签到 ,获得积分10
16秒前
Ava应助小殷采纳,获得10
16秒前
科研雪瑞发布了新的文献求助10
17秒前
格拉希尔完成签到,获得积分10
18秒前
18秒前
18秒前
和风发布了新的文献求助10
18秒前
19秒前
喜悦的板凳完成签到 ,获得积分10
19秒前
白菜包子完成签到,获得积分10
20秒前
想跟博哥打篮球完成签到,获得积分20
22秒前
轩海完成签到 ,获得积分10
22秒前
spinning发布了新的文献求助10
23秒前
23秒前
24秒前
白菜包子发布了新的文献求助10
25秒前
玉玉完成签到,获得积分10
29秒前
英姑应助白菜包子采纳,获得10
29秒前
30秒前
31秒前
31秒前
朴素小鸭子完成签到,获得积分10
33秒前
Zhao给Zhao的求助进行了留言
33秒前
Andy完成签到 ,获得积分10
34秒前
高分求助中
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
CLSI EP47 Evaluation of Reagent Carryover Effects on Test Results, 1st Edition 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
"Sixth plenary session of the Eighth Central Committee of the Communist Party of China" 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3055748
求助须知:如何正确求助?哪些是违规求助? 2712398
关于积分的说明 7431409
捐赠科研通 2357400
什么是DOI,文献DOI怎么找? 1248780
科研通“疑难数据库(出版商)”最低求助积分说明 606786
版权声明 596163