A comprehensive review of 3D manufacturing and process analytical technologies in pharmaceutical quality assurance

The assurance of pharmaceutical product quality, safety, and efficacy has historically relied on rigorous analytical standards, pharmacopoeial specifications, and the oversight of national and international regulatory authorities. While conventional regulatory frameworks and quality systems are well established for large-scale manufacturing, emerging technologies such as pharmaceutical three-dimensional printing (3DP) challenge existing paradigms, particularly in the context of personalized and small-batch drug production. Three-dimensional printing enables the fabrication of patient-specific dosage forms with tailored doses, geometries, and release profiles, offering significant advantages for paediatric, geriatric and patients experiencing polypharmacy. Despite its clinical promise, the widespread adoption of 3DP in pharmaceutical manufacturing remains constrained by fragmented regulatory guidance, limited pharmacopoeial standards, and insufficiently adapted quality assurance strategies. This review critically examines the current regulatory landscape governing pharmaceutical 3DP, with emphasis on the approaches adopted by major regulatory bodies, including the FDA, EMA, MHRA, and ICH. The evolving role of pharmacopoeias in defining quality requirements for 3D-printed dosage forms is discussed, alongside key regulatory milestones such as the approval of Spritam® and recent investigational products. Particular attention is given to the application of Quality by Design (QbD) and Process Analytical Technology (PAT) as systematic frameworks for identifying and controlling critical quality attributes, materials, and process parameters in additive manufacturing. Finally, the review highlights persistent regulatory and technical gaps and outlines considerations necessary for the harmonized integration of 3DP into pharmaceutical practice while ensuring product quality and patient safety.