Quality by design (QbD) approach in marketing authorization procedures of Non-Biological Complex Drugs: A critical evaluation

•The nature and diversity of Non-Biological Complex Drugs (NBCDs) bring new challenges to ensuring the reproducibility requirements, safety, and quality standards.•Quality by Design is a science and risk-based approach that allows a remarkable improvement in the design and control of the product and process, giving rise to a more robust, consistent, and high-quality drug product with a lower risk of market withdrawal.•A relatively small number of approved NBCDs present a marketing application based on the Quality by Design approach.•Lack of full-QbD submissions with an approved Design Space.•Design space is not a mandatory element, but presents unquestionable usefulness and operating flexibility in the post-approval change process, without the need for additional regulatory scrutiny.