Enabling the future of 3d-printed medicines : a systematic review

Abstract

Introduction: Additive Manufacturing (AM), leveraging 3D printing technology, offers transformative potential for producing personalized medicines on-demand directly at the point-of- care (POC). Despite this revolutionary promise, the translation of AM into regulated clinical practice is currently challenging. Key obstacles include fragmented regulatory frameworks, uncertain applicability of Good Manufacturing Practice (GMP) standards, and persistent knowledge gaps in risk and quality management within decentralized clinical settings.

Aims: • To synthesize and critically evaluate the principal challenges associated with implementing 3D printing for pharmaceutical drug products in decentralized settings (e.g., hospitals, pharmacies). • To examine emerging regulatory frameworks governing POC manufacturing, ultimately providing a comprehensive understanding of the regulatory, technical and practical factors necessary for the future integration of AM into pharmaceutical practice.

Method: Systematic Review - A rigorous systematic review was performed and reported according to PRISMA guidelines1 to ensure transparency. The comprehensive search, conducted in January 2025 across databases, focused on literature concerning the challenges and the GMP regulatory landscape of 3D printing of pharmaceutical drug products. Search sensitivity was assessed against benchmark studies, and titles and abstracts were screened by two reviewers to minimize bias. METHOD Inductive Thematic Analysis - Data analysis utilized inductive thematic analysis. All included studies were managed in NVivo 15, where a two- tiered descriptive coding scheme was manually applied to systematically categorize findings. Unique codes were clustered to create descriptive themes, which were then iteratively developed into analytical themes for higher-level conceptual interpretation. The emergent thematic framework was organized hierarchically, reflecting interconnections between structural, intermediate, and fundamental factors relevant to the research question.

Results: A three-tier framework was developed to classify interlinked barriers to AM adoption at decentralized sites: • Structural Level: Regulatory uncertainty, lack of harmonized standards, and limited readiness; emerging direction toward dedicated POC frameworks. • Intermediate Level: Operational and digital maturity gaps, compounding vs. manufacturing ambiguities, weak stakeholder collaboration, and ethical/legal/social complexities affecting scalability. • Fundamental Level: Sustainable integration depends on systemic readiness through adaptive regulation, robust quality infrastructure, decentralized pathways, and ethical, collaborative governance.

Conclusion: The barriers to adopting decentralized AM operate interdependently, clearly indicating that progress in one domain such as technical innovation, is insufficient without corresponding reform across others. Specifically, the successful implementation of hospital-based AM requires essential alignment between regulatory flexibility, digital readiness and ethical legitimacy. The developed framework emphasizes that technical advances alone cannot succeed without integrated policy and robust quality strategies. This work represents the first phase of a broader study that will address the multi-tiered gaps hindering Point-of-Care AM adoption by integrating risk analysis, Quality Management System (QMS) development, and feasibility modelling to provide a comprehensive framework for the safe and sustainable implementation of 3D-printed medicines.