Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a ‘zero’ preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders’ (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase.

在这里，我们建议扩展按设计质量（QbD）概念，使其也适合于药物的早期开发阶段，方法是添加当前被广泛应用但尚未以结构化方式包含在QbD模型中的元素。这些是“零”预配制阶段的引入（即，根据评估的治疗需要选择药物，可能的剂型和给药途径）；将利益相关者（行业，患者和法规）的要求纳入质量目标产品资料（QTTP）；以及在组成和过程设计阶段中使用现代质量管理工具[收集关键质量属性（CQA）和选择CPP）以进行（实验室规模的）设计空间（DS）开发。此外，在工业规模放大期间，CQA（以及关键的工艺参数；CPPs）可以更改；但是，我们建议在此阶段之后重新考虑并更新现有的QbD元素。