3D printing holds great promise to revolutionize pharmaceutical manufacturing, so for widespread clinical application, it is imperative to evaluate its safety and maximize its benefits. Herein, for the first time, particle emissions of the printing process of a model drug (fluorescein) were monitored in a test chamber to evaluate release. A filament extrusion-type 3D printer was used to make tablets from filaments loaded with fluorescein prepared by hot melt extrusion (HME) or diffusion (passive loading) techniques. Surface contamination of the printer was qualitatively documented. Average concentrations of fluorescein released into air during printing were below the analytical limit of detection for HME and 0.92 ± 0.20 ng/m(3) for diffusion. Particle yield from the aerodynamic particle sizer data (#/g extruded) during printing with HME filament (5.01 x 10(4)) was significantly lower (p < 0.05) compared with diffusion filament (1.07 x 10(6)). Mathematical modeling was used to predict where particles might deposit in the respiratory system if inhaled by a worker. Predictions showed larger fractions of particles deposited in the head and pulmonary (alveolar) regions from diffusion-loaded filament compared with HME, albeit non-significant. Fluorescein was transferred onto personal protective equipment (gloves) and printer surfaces, which indicated potential for dermal exposure and cross-contamination. Assuming our results are representative of active pharmaceutical ingredients, they support the importance of controls such as containment to minimize inhalation exposure and housekeeping to minimize dermal exposure and cross-contamination of tablets.

Vat photopolymerization (VP) is an additive manufacturing process that uses light to harden resin and build a 3-dimensional shape. Stereolithography (SLA) printing is a variant of VP that uses a laser beam as the light source to initiate a polymerization reaction. During SLA printing, particles and gases can be emitted into the air; however, factors that influence emissions are poorly understood for this technology. Emissions from two brands of SLA printers from different manufacturers (herein termed A and B) were measured using real-time (particle number and size, total volatile organic compound [TVOC] concentration) and time-integrated (aldehydes, acrylates, aromatics, alkanes, butylated hydroxy toluene, and elements) techniques in an environmental test chamber. Three colors of resins (black, clear, and gray), all from the same manufacturer, were tested on each printer. All statistical comparisons used a significance level of 0.05. Printer brand strongly influenced the emission yields. Printer A had significantly higher particle number yield, smaller particle size, and higher 2-hydroxyethyl methacrylate (2-HEMA) and 2-hydroxypropyl methacrylate yields for all resin colors compared with printer B. There were also significant differences between brands in yield values for several aldehydes (acetaldehyde, butyraldehyde, hexaldehyde, isovaleraldehyde, o,m,p-tolualdehyde, and propionaldehyde). Resin color had a minor influence on yields for particle number, some aldehydes, and 2-HEMA for printer A only. The strong influence of printer brand on emissions was partially explained by printer configuration, i.e., printer A had a built-in resin heater, whereas printer B did not. Emission yields of organic chemicals were not always higher for printer A compared with printer B, which indicated that other factors also influenced emissions. Improved understanding of factors that influence emissions from SLA printers is critical for developing exposure mitigation strategies using a hierarchy of controls. Not subject to U.S. Copyright. Published 2025 by American Chemical Society.