• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biotechnology Progress >Development of Downstream Processing to Minimize Beta-Glucan Impurities in GMP-Manufactured Therapeutic Antibodies
【24h】

Development of Downstream Processing to Minimize Beta-Glucan Impurities in GMP-Manufactured Therapeutic Antibodies

机译：在GMP生产的治疗性抗体中使β-葡聚糖杂质最小化的下游加工技术的发展

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The presence of impurities or contaminants in biological products such as monoclonal antibodies (mAb) could affect efficacy or cause adverse reactions in patients. ICH guidelines (Q6A and Q6B) are in place to regulate the level of impurities within clinical drug products. An impurity less often reported and, therefore, lacking regulatory guideline is beta-glucan. Beta-glucans are polysaccharides of D-glucose monomers linked by (1-3) beta-glycosidic bonds, and are produced by prokaryotic and eukaryotic organisms, including plants. They may enter manufacturing processes via raw materials such as cellulose-based membrane filters or sucrose. Here we report the detection of beta-glucan contamination of a monoclonal IgE antibody (MOv18), manufactured in our facility for a first-in-human, first-in-class clinical trial in patients with cancer. Since beta-glucans have potential immunostimulatory properties and can cause symptomatic infusion reactions, it was of paramount importance to identify the source of beta-glucans in our product and to reduce the levels to clinically insignificant concentrations. We identified beta-glucans in sucrose within the formulation buffer and within the housing storage buffer of the virus removal filter. We also detected low level beta-glucan contamination in two of four commercially available antibodies used in oncology. Both formulation buffers contained sucrose. We managed to reduce levels of beta-glucan in our product 10-fold, by screening all sucrose raw material, filtering the sucrose by Posidyne VR membrane filtration, and by incorporating extra wash steps when preparing the virus removal filter. The beta-glucan levels now lie within a range that is unlikely to cause clinically significant immunological effects. (C) 2016 American Institute of Chemical Engineers
机译：诸如单克隆抗体（mAb）之类的生物产品中存在杂质或污染物可能会影响疗效或引起患者不良反应。制定了ICH指南（Q6A和Q6B）来调节临床药物产品中的杂质水平。 β-葡聚糖是一种较少报道的杂质，因此缺乏法规指导。 β-葡聚糖是通过（1-3）β-糖苷键连接的D-葡萄糖单体的多糖，由原核和真核生物（包括植物）产生。它们可能通过诸如纤维素膜过滤器或蔗糖之类的原材料进入制造过程。在这里，我们报告了检测到的单克隆IgE抗体（MOv18）的β-葡聚糖污染的情况，该抗体是在我们的工厂中生产的，用于癌症患者的首次人类一流临床试验。由于β-葡聚糖具有潜在的免疫刺激特性，并可能引起症状性输注反应，因此，确定我们产品中β-葡聚糖的来源并将其水平降低至临床上不重要的浓度至关重要。我们在配方缓冲液中和病毒去除过滤器的外壳存储缓冲液中鉴定出蔗糖中的β-葡聚糖。我们还在肿瘤学中使用的四种市售抗体中的两种中检测到低水平的β-葡聚糖污染。两种制剂缓冲液均包含蔗糖。通过筛选所有蔗糖原料，通过Posidyne VR膜过滤法过滤蔗糖，以及在准备除病毒过滤器时采用额外的洗涤步骤，我们设法将产品中的β-葡聚糖含量降低了10倍。现在，β-葡聚糖水平处于不太可能引起临床上明显的免疫学影响的范围内。 （C）2016美国化学工程师学会

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号