Enhancing Pharmaceutical 3D Printing through Quality-by-Design (QbD): Challenges, Strategies, and Regulatory Insights

Pharmaceutical 3D printing (3DP) is a rapidly advancing manufacturing platform that enables the development of patient-specific dosage forms with tailored drug release profiles. Despite its transformative potential, challenges such as process variability, material compatibility, and regulatory ambiguity have hindered its widespread adoption. This review presents an integrated framework for applying Quality by Design (QbD) principles to 3DP, addressing key quality concerns through systematic identification and control of Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs). Risk assessment tools such as Design of Experiments (DoE) and Failure Mode and Effects Analysis (FMEA) are explored to optimize printing parameters and ensure robust manufacturing processes. Real-time monitoring and digital quality control methods are highlighted as emerging solutions for ensuring batch-to-batch consistency and regulatory compliance. Furthermore, this paper outlines the current regulatory landscape, compares agency-specific guidelines, and proposes a structured QbD workflow tailored for pharmaceutical 3DP. By bridging scientific rigor with manufacturing innovation, the proposed framework aims to advance the scalability, quality, and personalization of drug therapies.