University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, H-6720 Szeged, Eötvös u. 6, Hungary.
University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, H-6720 Szeged, Eötvös u. 6, Hungary.
Drug Discov Today. 2018 Jul;23(7):1340-1343. doi: 10.1016/j.drudis.2018.03.012. Epub 2018 Mar 27.
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，我们提出将质量源于设计（QbD）概念扩展到制药的早期开发阶段，通过添加目前广泛应用但尚未以结构化方式纳入 QbD 模型的元素。这些元素包括引入“零”预配方阶段（即根据评估的治疗需求选择药物物质、可能的剂型和给药途径）；将利益相关者（行业、患者和监管机构）的要求纳入质量目标产品概况（QTTP）；以及在组成和工艺设计阶段使用现代质量管理工具[收集关键质量属性（CQAs）并选择（仍处于实验室规模的）设计空间（DS）开发的 CPPs]。此外，在工业放大过程中，CQAs（以及关键工艺参数；CPPs）可能会发生变化；但是，我们建议在该阶段之后重新考虑和更新现有的 QbD 元素。
