Additive manufacturing of microneedles: a quality by design approach to clinical translation

Transdermal drug delivery systems (TDDS) offer a painless and non-invasive route of administration but are limited by the skin barrier. Microneedles (MNs) have been shown to overcome this challenge and enable the delivery of small molecules, peptides and biologics. Recent advances in the field of additive manufacturing (AM), particularly three-dimensional printing, have facilitated precise control of the geometry, materials and drug loading strategies of MNs, thereby enhancing scalability and reproducibility. In this context, a Quality by Design (QbD) framework is employed to ensure consistent product quality by defining Critical Quality Attributes (CQAs) and utilising risk management tools such as Ishikawa diagrams and Failure Mode and Effects Analysis (FMEA). Artificial Intelligence (AI) is emerging as a complementary tool to QbD, enabling predictive modeling and process optimization in MN manufacturing. Despite the progress that has been made, regulatory guidelines continue to be underdeveloped. However, the FDA, EMA and other international authorities are working towards harmonisation. The clinical applications of MNs are expanding rapidly, with ongoing studies in the areas of vaccination, diabetes, cancer therapy and migraine. This review integrates current knowledge of AM technologies, QbD-guided strategies, materials, regulatory issues, and clinical perspectives that are shaping the future of MN drug delivery.