Zwiers Regulatory Consultancy, Pivot Park, Kloosterstraat 9, 5349AB, Oss, The Netherlands.
Ther Innov Regul Sci. 2021 May;55(3):583-590. doi: 10.1007/s43441-020-00254-9. Epub 2021 Jan 13.
Quality by Design (QbD) is a systematic risk-based approach to development, with predefined characteristics and quality risk management throughout the life cycle of a product. International Conference on Harmonization (ICH) guidelines Q8-Q11 give guidance on QbD applications with ICH Q8 (R2)-approved in 2009-describing the principles of QbD in detail. Since its adoption over 10 years ago, more information about QbD usage for the development of medicinal products is expected to be written in regulatory dossiers by companies.
The present study set out to evaluate the implementation of QbD principles and elements in all EU approved marketing applications (MA) (n = 494), based on information available in the European Public Assessment Reports (EPARs), for a period of six years (2014-2019), starting 5 years after QbD adoption.
Of the 494 MAs, 271 were submitted with a full dossier (article 8(3)). According to EMA (38%), out of the 271 full dossier submissions, only 104 were developed using full QbD. This figure did not increase during this period. Interestingly, between 2014 and 2019, several MAs were not developed via full QbD implementation but used one or more QbD elements during development, including design space. In addition, a higher percentage of small molecule products were developed with QbD as opposed to biotechnology-derived products (78% vs. 22%, respectively).
Overall, QbD during development of medicinal products is still not commonly described in dossiers. However, more companies started mentioning QbD elements, thus making it a promising step toward QbD as the standard for development in the future.
质量源于设计（QbD）是一种基于系统风险的方法，在产品的整个生命周期中都具有预定义的特性和质量风险管理。国际人用药品注册技术协调会（ICH）指南 Q8-Q11 提供了关于 QbD 应用的指导，ICH Q8（R2）于 2009 年批准——详细描述了 QbD 的原则。自 10 多年前采用以来，预计公司在监管档案中会有更多关于 QbD 在药品开发中的应用的信息。
本研究旨在评估在六年期间（2014-2019 年），从 QbD 采用后五年开始，根据欧洲公共评估报告（EPAR）中提供的信息，在所有欧盟批准的上市申请（MA）（n=494）中实施 QbD 原则和要素的情况。
在 494 份 MA 中，有 271 份是完整档案提交的（第 8（3）条）。根据 EMA（38%）的说法，在 271 份完整档案提交中，只有 104 份是使用完整 QbD 开发的。在此期间，这一数字并没有增加。有趣的是，在 2014 年至 2019 年期间，有几个 MA 并非通过全面实施 QbD 开发，而是在开发过程中使用了一个或多个 QbD 要素，包括设计空间。此外，小分子产品的开发采用 QbD 的比例高于生物技术衍生产品（分别为 78%和 22%）。
总体而言，在药品开发过程中 QbD 仍未在档案中普遍描述。然而，越来越多的公司开始提及 QbD 要素，因此这是朝着未来将 QbD 作为开发标准迈出的有希望的一步。
