Junker Beth, Kosinski Mike, Geer David, Mahajan Rajiv, Chartrain Michel, Meyer Brian, Dephillips Peter, Wang Yang, Henrickson Randy, Ezis Katie, Waskiewicz Mark
Bioprocess Development, Vaccines Research and Pre-Clinical Development, Biologics Manufacturing Sciences & Commercialization, Global Vaccines Technology and Engineering/Global Biologics Quality, Merck and Co, Inc.
PDA J Pharm Sci Technol. 2011 May-Jun;65(3):254-86. doi: 10.5731/pdajpst.2011.00739.
An initial quality-by-design (QbD) framework was assembled for biopharmaceutical product, process, and analytical development using the design-for-six-sigma (DFSS) methodology. This technique was both streamlined and efficient, which permitted development of a QbD framework with minimized team leader and member resources. DFSS also highly emphasized voice-of-the-customer, information considered crucial to development and implementation of a bioprocess QbD framework appropriate for current development needs of the organization and its regulatory environment. The bioprocess QbD final design and implementation plan was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the QbD charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation.
An initial quality-by-design (QbD) framework was assembled to guide biopharmaceutical product, process, and analytical development. QbD starts by defining the patient requirements which then are translated into required quality attributes for the product. The production process then is designed to consistently meet these quality requirements by identifying and understanding those parameters which influence them. A control strategy is developed that specifically relates each point of control to a desired quality measure. Overall, this approach results in a robust process, capable of reliably producing quality product. The bioprocess QbD framework was developed to guide implementation of the desired QbD strategy. It was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation.
使用六西格玛设计（DFSS）方法为生物制药产品、工艺和分析开发构建了一个初始的质量源于设计（QbD）框架。该技术既精简又高效，使得能够以最少的团队领导和成员资源开发出一个QbD框架。DFSS还高度强调客户声音，这一信息对于开发和实施适合组织当前发展需求及其监管环境的生物工艺QbD框架至关重要。生物工艺QbD最终设计和实施计划由七个团队组成，由六个QbD要素加上一个沟通/培训团队构建而成。根据内部和外部既定的最佳实践、QbD章程和设计输入对每个要素的详细设计进行评估。识别差距并减轻风险，以确保所提议框架的稳健性。估计汇总资源和时间安排以获得关键的实施支持。在可能的情况下，利用现有的治理和信息技术工作，以尽量减少所需的额外生物工艺资源。最后，选择指标来跟踪试点和最终实施的成功情况。
构建了一个初始的质量源于设计（QbD）框架来指导生物制药产品、工艺和分析开发。QbD首先定义患者需求，然后将其转化为产品所需的质量属性。然后设计生产工艺，通过识别和理解影响这些质量要求的参数来始终如一地满足这些要求。制定一种控制策略，将每个控制点具体关联到期望的质量度量。总体而言，这种方法产生一个稳健的工艺，能够可靠地生产出高质量产品。生物工艺QbD框架旨在指导所需QbD策略的实施。它由七个团队组成，由六个QbD要素加上一个沟通/培训团队构建而成。根据内部和外部既定的最佳实践、章程和设计输入对每个要素的详细设计进行评估。识别差距并减轻风险，以确保所提议框架的稳健性。估计汇总资源和时间安排以获得关键的实施支持。在可能的情况下，利用现有的治理和信息技术工作，以尽量减少所需的额外生物工艺资源。最后，选择指标来跟踪试点和最终实施的成功情况。
