Multistage continuous countercurrent diafiltration for formulation of monoclonal antibodies

Jabra Mario G.; Yehl Christopher J.; Zydney Andrew L.

摘要

Abstract > There is growing interest in the development of fully integrated and continuous biomanufacturing processes for the production of monoclonal antibody products. A recent study has demonstrated the feasibility of using a two‐stage countercurrent diafiltration (DF) process for continuous product formulation, but this system did not provide sufficient levels of buffer exchange for most applications. The objective of this study was to design and test a three‐stage countercurrent DF system that could achieve at least 99.9% buffer exchange over 24?hr of continuous operation. Experimental data were obtained using concentrated solutions of human immunoglobulin G as a model protein, with the extent of vitamin B <sub>12</sub> removal used to track the extent of DF. Pall Cadence? inline concentrators with Delta 30?kD regenerated cellulose membranes were used in the three stages to achieve high conversion in a single pass. The three‐stage system showed stable operation with 99.9% vitamin B <sub>12</sub> removal and a minimal increase in pressure over the full 24?hr. Modules were effectively cleaned using sodium hydroxide, with nearly complete recovery of water permeability. A simple economic analysis was presented that accounts for the trade‐offs between quantity of buffer used and membrane costs for this type of countercurrent staged DF process. The results provide important insights to the design and operation of a continuous process for antibody formulation. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 对生产单克隆抗体产物的完全集成和连续生物制造工艺的开发越来越感兴趣。最近的一项研究表明，使用两阶段逆流渗滤（DF）方法进行连续产品配方的可行性，但该系统没有为大多数应用提供足够的缓冲液交换。本研究的目的是设计和测试一个三阶段逆流DF系统，可以达到至少99.9％的缓冲交换超过24？小时的连续操作。使用人免疫球蛋白G作为模型蛋白的浓缩溶液获得实验数据，维生素B的程度 <sub> 12 </ sub> 去除用于跟踪DF的程度。 PALL CADENCES？三个阶段使用具有Delta 30的内联浓缩器30？KD再生纤维素膜在一次通过中达到高转化。三阶段系统与＆ 99.9％维生素B稳定运行 <sub> 12 </ sub> 完全24的拆除和压力的最小增加。使用氢氧化钠有效地清洁模块，具有几乎完全恢复的水渗透性。提出了一个简单的经济分析，占这种类型的逆流分阶段DF过程的缓冲液数量和膜成本之间的权衡。结果为抗体制剂的连续方法的设计和操作提供了重要的见解。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15005/'>《Biotechnology Progress》</a> <b style="margin: 0 2px;">|</b><span>2019年第4期</span><b style="margin: 0 2px;">|</b><span>共6页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jabra Mario G.&option=202" target="_blank" rel="nofollow">Jabra Mario G.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yehl Christopher J.&option=202" target="_blank" rel="nofollow">Yehl Christopher J.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zydney Andrew L.&option=202" target="_blank" rel="nofollow">Zydney Andrew L.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Chemical EngineeringThe Pennsylvania State UniversityUniversity Park Pennsylvania;</p> <p>Department of Chemical EngineeringThe Pennsylvania State UniversityUniversity Park Pennsylvania;</p> <p>Department of Chemical EngineeringThe Pennsylvania State UniversityUniversity Park Pennsylvania;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/15.html" title="生物科学">生物科学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=antibody&option=203" rel="nofollow">antibody;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=continuous processing&option=203" rel="nofollow">continuous processing;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=countercurrent staging&option=203" rel="nofollow">countercurrent staging;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=diafiltration&option=203" rel="nofollow">diafiltration;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=formulation&option=203" rel="nofollow">formulation;</a> </p> <div class="translation"> 机译：抗体;连续加工;逆流分期;渗滤;制剂; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity 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G.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Sieckmann, D. G.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext= Stall, A. M.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> Stall, A. M.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext= Subbarao, B.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> Subbarao, B. </a> <span>1991</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：小鼠单克隆抗体特异性针对Igh（a）小鼠Igm等位基因的同种型决定因素：使用抗Igm单克隆抗体的Igh-6a表位的遗传和功能分析。</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-east-china-university-science-technology-natural-edition_thesis/0201293623709.html">Process of Continuous Multistage Countercurrent Fractional Crystallization for 4-Nitrochlorobenzene and 2-Nitrochlorobenzene（摘要）</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=LI Qun-sheng YI Zheng-ming&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . LI Qun-sheng YI Zheng-ming</a> <span> <a href="/journal-cn-50120/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 华东理工大学学报：自然科学版 </a> </span> <span> . 2011</span><span>,第1期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-cancer-research-english_thesis/0201296816002.html">PRODUCTION AND APPLICATION OF MONOCLONAL ANTIBODY TO POLYAMINE (PREPARATION AND CHARACTERISTICS OF MONOCLONAL ANTIBODIES AGAINST SPERMIDINE)</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王德斌&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 王德斌</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=陈智周&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,陈智周</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=范振符&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,范振符</a> <span> <a href="/journal-cn-52929/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国癌症研究：英文版 </a> </span> <span> . 1991</span><span>,第4期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020315812433.html">Cloning and expression of p32 gene of sheep poxvirus and its preparation of monoclonal antibody</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shura Gansukh&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . Shura Gansukh</a> <span> . 2019</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06130452670795.html">Preparation of monoclonal antibody for administration to a human pharmaceutical formulation use of a monoclonal antibody preparation and process for the manufacture of a monoclonal antibody preparation</a> <b>[P]</b> . <span> 外国专利：  BR9709267A </span> <span> . 1999-08-10</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：单克隆抗体制剂的向人用药物制剂给药的单克隆抗体的制备以及单克隆抗体制剂的制造方法 </span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06130432835030.html">peptide, nucleic acid chain, pharmaceutical formulation, vaccine formulation, monoclonal antibody and uses of peptide and monoclonal antibody</a> <b>[P]</b> . <span> 外国专利：  BRPI0515403A </span> <span> . 2008-07-22</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：肽，核酸链，药物制剂，疫苗制剂，单克隆抗体以及肽和单克隆抗体的用途 </span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130406782534.html">Stable aqueous pharmaceutical formulation, article, methods for stabilizing an antibody, for treating a disease or disorder in an individual, for reducing aggregation of a therapeutic monoclonal antibody and for manufacturing a pharmaceutical formulation, vial and stainless steel tank</a> <b>[P]</b> . <span> 外国专利：  BR112012013093A2 </span> <span> . 2017-12-12</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：稳定的水性药物制剂，物品，用于稳定抗体，用于治疗个体的疾病或病症，用于减少治疗性单克隆抗体的聚集以及用于制备药物制剂的药水，小瓶和不锈钢罐 </span> </p> </li> </ul> </div> </div> </div> <div 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