Abstract Quality by Design is a recent concept from quality control which has led to new requirements demanded by the authorities, particularly in the pharmaceutical industry. Among these, the guideline ICHQ8 explains that quality cannot be tested into products but should be built in by design. Designs of Experiments have been used to establish the relationship between input and output parameters of a process or formula while minimizing the risk in the final decision. More precisely, modelling studies are carried out to better understand the process and to predict the outputs in the whole domain of interest. When there are many input and output parameters, the experimenter looks for a compromise zone in which all the output parameters comply with the specifications. In this area, we can define a region where all the inputs can vary without altering the quality of the product with a fixed probability that the objectives will be reached. This zone is called Design Space and the determination of their boundaries is recommended by the Food and Drug Administration. In this publication, we propose different methods such as Monte-Carlo method, Bootstrap technique, numerical approach and reliability method to determine the Design Space. A comparison study is achieved using a case study.

中文翻译：

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质量源于设计：实验设计案例中设计空间构建方法的比较

摘要 质量源于设计是质量控制的最新概念，它导致当局提出了新的要求，尤其是在制药行业。其中，ICHQ8 指南解释了质量不能测试到产品中，而应通过设计内置。实验设计已被用于建立过程或公式的输入和输出参数之间的关系，同时最大限度地降低最终决策中的风险。更准确地说，进行建模研究是为了更好地理解过程并预测整个感兴趣领域的输出。当输入和输出参数很多时，实验者寻找一个折衷区域，其中所有输出参数都符合规范。在这个领域，我们可以定义一个区域，所有输入都可以在不改变产品质量的情况下以固定的概率实现目标。该区域称为设计空间，食品和药物管理局建议确定其边界。在本出版物中，我们提出了不同的方法，例如蒙特卡罗方法、Bootstrap 技术、数值方法和可靠性方法来确定设计空间。使用案例研究进行比较研究。确定设计空间的数值方法和可靠性方法。使用案例研究进行比较研究。确定设计空间的数值方法和可靠性方法。使用案例研究进行比较研究。