Quality by Design and Process Analytical Technology for On-Demand Drug Manufacturing Through 3D Printing.

Additive manufacturing, also known as 3D printing (3DP), is intended to enable personalised medicine by producing drug products on demand at the Point of Care (PoC), with dose, drug-release profile, and geometry tailored to the individual patient. Despite its promise, widespread adoption is limited by the absence of ready-to-use quality control (QC) methods for printlets at the PoC. Process Analytical Technology (PAT) tools, particularly vibrational spectroscopic methods like Near-Infrared and Raman spectroscopy, can offer real-time monitoring to ensure the safety and consistency of printed dosage forms. Integrating these tools within a Quality-by-Design (QbD) framework can enhance process understanding, control variability, and minimise risk. Regulatory implementation and technological innovation remain essential for the broader clinical implementation of 3DP in pharmaceutical manufacturing. This review presents an overview of currently existing studies on PAT tools explored for non-destructive quality control across 3DP techniques, examines the correlation between Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), and the Critical Quality Attributes (CQAs) of 3D-printed dosage forms within a QbD context, and outlines the current regulatory landscape alongside key limitations and future directions for the broader integration of 3DP into pharmaceutical development and manufacturing. Current evidence shows that PAT application remains uneven across printing technologies and is predominantly directed at final product quality control, rather than the real-time process monitoring required for a fully closed-loop QbD framework. Existing spectroscopic models are largely restricted to single formulations, printers, and APIs, and the absence of standardised validation reporting and transferability assessments represents a key barrier to routine implementation.