Quality Assurance in Decentralized Manufacturing: A Review of Validation Frameworks for 3D-Printed Personalized Medicines

Background The pharmaceutical industry is in a paradigm shift in which the mass-production model based on one-size-fits-all is being replaced by the patient-centric model that is made possible by three-dimensional printing (3DP) and decentralized manufacturing (DM). Although 3DP enables the personalization of dosage form as never before, the translation of the technology into clinical practice is complicated by the complicated quality assurance (QA) and validation barriers. Purpose: This review critically synthesizes the existing validation frameworks of 3DP personalized medicines with special emphasis on the combination of Process Analytical Technology (PAT), Digital Twins, and the recently implemented UK MHRA 2025 regulatory framework. Methodology: Scopus-indexed literature (20192026) was searched in a PRISMA-compliant systematic search that focused on point-of-care (POC) manufacturing, real-time release testing (RTRT), and data integrity. Core Mechanisms: We consider technical modalities, such as Fused Deposition Modeling (FDM), Semi-Solid Extrusion (SSE), and Selective Laser Sintering (SLS), their respective Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs). Findings: The review identifies the Hub-and-Spoke model as the most feasible structure of decentralized QA with centralized hubs that address the issue of integrity of the pharma-ink and decentralized spokes that address the issue of process validation. In-line Near-Infrared (NIR) and Raman spectroscopy technologies that enable the real time release of doses are accurate and non-destructive (R 2 = 0.98) and allow real time verification of doses. Moreover, the Digital Twin technology improves three-stage process validation lifecycle, providing predictive maintenance and proactive quality management. Conclusion: To attain sustainable clinical implementation of the 3DP, a radical change toward Quality-by-Design (QbD) and a powerful digital infrastructure is required. In the coming 2026 and beyond, we suggest a roadmap to standardize decentralized validation to achieve the best safety and efficacy of personalized medicines.