Process characterization and Design Space definition
Process characterization and Design Space definition
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DOI：
10.1016/j.biologicals.2016.06.004
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发表时间：
2016-09-01
期刊：
影响因子：
1.7
通讯作者：
Wurth, Christine
中科院分区：
文献类型：
--
作者：
Hakemeyer, Christian;McKnight, Nathan;Wurth, Christine
质量源于设计（QbD）是一项全球监管举措，旨在通过积极设计药品生产工艺和控制来加强药品开发，以始终如一地提供产品的预期性能。与QbD相关的药物开发原则见ICH指导文件（ICHQ 8 -11）。Roche/Genentech开发的一套完整的风险评估及其相关要素旨在概述重组单克隆抗体（MAb）生产的产品和工艺知识，本章描述了QbD范式下用于MAb生产工艺表征和验证的工具。这包括用于确定潜在关键工艺参数（pCPP）的风险评估、统计学设计的实验研究以及评估单元操作之间联系的研究。研究结果是根据关键性对工艺参数进行分类，并定义适当的可接受操作范围。在这些研究中获得的过程和产品知识可以导致设计空间的批准。此外，这些研究中获得的信息用于定义生产工艺对CQA变异性的“影响”，CQA变异性用于定义检测和监测策略。(C)2016年国际生物标准化联盟。由爱思唯尔有限公司出版。保留所有权利。
Quality by design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody (MAb).This chapter describes the tools used for the characterization and validation of MAb manufacturing process under the QbD paradigm. This comprises risk assessments for the identification of potential Critical Process Parameters (pCPPs), statistically designed experimental studies as well as studies assessing the linkage of the unit operations. Outcome of the studies is the classification of process parameters according to their criticality and the definition of appropriate acceptable ranges of operation. The process and product knowledge gained in these studies can lead to the approval of a Design Space. Additionally, the information gained in these studies are used to define the 'impact' which the manufacturing process can have on the variability of the CQAs, which is used to define the testing and monitoring strategy. (C) 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.