Hakemeyer Christian, McKnight Nathan, St John Rick, Meier Steven, Trexler-Schmidt Melody, Kelley Brian, Zettl Frank, Puskeiler Robert, Kleinjans Annika, Lim Fred, Wurth Christine
Pharma Technical Development, Roche Diagnostics GmbH, Sandhofer Str. 116, 68305 Mannheim, Germany.
Pharma Technical Development, Genentech, South San Francisco, CA 94080, USA.
Biologicals. 2016 Sep;44(5):306-18. doi: 10.1016/j.biologicals.2016.06.004. Epub 2016 Jul 25.
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.
质量源于设计（QbD）是一项全球监管举措，其目标是通过对制药生产工艺和控制进行前瞻性设计，以持续实现产品预期性能，从而加强药物研发。与QbD相关的药物研发原则在国际人用药品注册技术协调会（ICH）指导文件（ICHQ8 - 11）中有描述。罗氏/基因泰克公司制定的一套综合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。本章描述了在QbD范式下用于单克隆抗体制备工艺表征和验证的工具。这包括用于识别潜在关键工艺参数（pCPPs）的风险评估、统计设计的实验研究以及评估单元操作之间联系的研究。这些研究的结果是根据工艺参数的关键性对其进行分类，并定义适当的可接受操作范围。这些研究中获得的工艺和产品知识可促成设计空间的批准。此外，这些研究中获得的信息用于定义生产工艺对关键质量属性（CQA）变异性可能产生的“影响”，这用于定义测试和监测策略。
